the compulsive drive to use a substance in spite of the adverse consequences involved. Addiction meets at least one of the “five Cs” of drug using behavior: the drug is used chronically, compulsively, disregarding the consequences of use; the user craves the drug, and lacks control over use of the drug.
a false, fixed belief (often an aspect of psychosis). Patients may believe that they are a historical figure, that someone is persecuting them, or that they have special powers, among other ideas.
the condition of needing to take a medication to avoid symptoms of withdrawal. Although this is a common symptom in people who use drugs or alcohol recreationally, this may also be a feature of some drugs used for high blood pressure, depression, and pain. Dependence should not be confused with addiction, which involves psychological and motivational drives to use a drug.
a false sensory experience, such as hearing, seeing, smelling, or feeling something that is not really there. Hallucinations may be a symptom of a psychotic condition, such as schizophrenia, or a result from a drug reaction or medical condition, such as delirium.
the state of agitation associated with bipolar disorder, in which a patient may feel abnormally energetic, excited, creative, and irritable. Manic episodes can also include psychotic symptoms.
a medication that is prescribed to keep a patient with bipolar disorder from swinging into either mania or depression.
the fear of an object, situation, or living thing, such as arachnophobia (the fear of spiders).
a condition in which a patient’s experiences are not in agreement with objective reality (eg, hallucinations and delusions).
the intentional taking of one’s own life. Suicide and suicide attempts are more common in patients with psychiatric illnesses, such as depression, bipolar disease, and schizophrenia, than in the general population.
the phenomenon of requiring larger doses of a drug to get the same effect that was previously achieved by a lower dose. Tolerance can apply to both the desired and undesired effects of a medication. Although people who take drugs recreationally often become tolerant to the drug’s effects, tolerance by itself is not the same as addiction.
After completing this chapter, you should be able to
Recall what is known of the causes and prevalence of mental illnesses.
List the symptoms and recall the expected course of the following illnesses:
Attention deficit hyperactivity disorder.
Substance use disorder.
Recognize the psychosocial consequences for patients and families of patients with psychiatric disorders.
State the generic and brand names of medications used to treat psychiatric disorders, along with dosage forms and available doses.
Discuss the mechanism of action, common adverse effects, and special precautions of medications used to treat psychiatric disorders.
Psychiatric disorders hold a special place in medicine. These disorders, for the most part, cannot be detected or monitored using blood tests, x-rays, or any number of diagnostic procedures in the way other medical problems are. Symptoms of these disorders are expressed in terms of emotions and behaviors. Patients with psychiatric conditions sometimes appear eccentric, disorderly, or peculiar. They are at a higher risk of early death due to violence and suicide. Along with patients with neurologic diseases, people with psychiatric diagnoses are burdened with stigma. Stigma is the condition of associating negative attitudes with a person due to a characteristic that person carries. The stigma of psychiatric disorders can cause delays in diagnosis and adherence to treatment. Psychiatric patients are sometimes blamed for their conditions, believed to be morally lacking, and told that they are weak. Patients are subjected to scrutiny and judgment that those with other medical conditions, such as diabetes and cancer, do not have to deal with.
These attitudes are unfortunate because psychiatric illnesses are caused by processes going wrong in the brain. These problems are usually caused by some abnormality in the chemical messengers that carry nerve signals around the brain and to other parts of the body. These chemical messengers, the neurotransmitters described in Chapters 4 and 5, are the targets of many of the medications used to treat mental illnesses. Neurotransmitters have different effects when their activity is either too high or too low. We know that neurotransmitters are involved in different psychiatric illnesses. In addition, other brain chemicals and chemical receptors have an effect on the way the brain processes information, moods, and perceptions. Often, a patient will have more than one psychiatric diagnosis at the same time. Due to the vast differences from one patient to another and the lack of a physical means of measuring brain chemical levels, doctors may need to try different medications to find the one that works best for a patient that is also well tolerated. For these reasons, treating psychiatric illnesses is often quite challenging.
Many psychiatric diseases tend to run in families, suggesting a genetic component. Some, such as schizophrenia, have genetic trends but may also occur in a family previously unaffected by the disease. Interestingly, many famous artists, musicians, writers, inventors, and scientists have suffered from psychiatric diseases. Although at times patients with psychiatric illnesses do not have the insight necessary to maintain good adherence to their therapy, members of their healthcare team need to apply empathy as well as good judgment in dealing with them. Patients need to know that their pharmacy team members are trustworthy, nonjudgmental, and concerned. With more openness and acceptance, individuals may find it easier to open up about concerns about themselves or family members. Psychiatric symptoms such as anxiety, depression, and delusions can also be side effects of medications and systemic medical problems. In addition, psychiatric conditions, such as depression and anxiety, can accompany many chronic medical problems.
Who treats patients with psychiatric illnesses? There are many practitioners who treat these patients. In most states, only physicians can prescribe medications for psychiatric illnesses. Of these physicians, the most commonly associated with these illnesses are psychiatrists. Psychiatrists are physicians who specialize in diagnosing and treating mental illnesses. Other practitioners include psychologists, psychiatric social workers, and various therapists, who provide counseling to help patients understand and manage their illnesses. However, most patients are treated by non-specialists, including family physicians, internists, and pediatricians. Nurse practitioners, physician’s assistants, and psychiatric pharmacists also provide care under a physician’s supervision.
Because psychiatric illnesses can’t be detected or monitored with thermometers, stethoscopes, and x-rays, psychiatrists have developed diagnostic criteria for each illness that are gathered together in the Diagnostic and Statistical Manual of Mental Disorders.1 This book is in its fifth edition and is referred to as the DSM-5. The DSM-5 lists characteristics and symptoms for each identified mental disorder and gives the criteria needed for diagnosing an illness. Many other diagnostic and assessment tools, such as the Mental Status Examination, the Hamilton Depression Inventory, and the Positive and Negative Symptom Scale are used to determine, measure, and monitor mental illnesses. During the interview with the patient, the practitioner will determine where the patient’s symptoms fit among various potential diagnoses. The practitioner considers the patient’s current symptoms, including mood, activity level, interests, behavior, appearance, and thought processes, and also the patient’s personal and family history. The doctor will rate the patient’s level of insight into the situation and whether the patient appears to have the potential to be dangerous to him- or herself or others. Some of the traits assessed are mood, affect, facial expressiveness, appearance, use of language, activity, thought disturbances, insight, and judgment. The practitioner will also consider whether the symptoms could be due to medication side effects or another illness. For example, when thyroid hormone levels are low, a patient will often feel tired and depressed, so when a person complains of depression, thyroid gland function will usually be checked.
When a diagnosis is made, a course of treatment will also be planned. This is frequently done in collaboration with the patient and sometimes with other family members. In some situations, there may be more than one reasonable alternative, such as medication or counseling. Medication is often necessary for the patient to be restored to a reasonable level of functioning. In most situations, counseling is also beneficial to help the patient learn to manage his or her illness.
Justine is a 36-year-old married woman who has gone to her doctor because she is having trouble sleeping and cannot concentrate on her work as a data entry technician. When the doctor questioned her, she also admitted that she and her husband have recently separated, her mother died 6 months ago, and she is having trouble with her 14-year-old daughter. Justine says that she has to make a lot of effort just to get out of bed and get ready for work, has frequent crying spells, and she does not have hope of her life getting better. She has stopped going to her quilting class and choir practice because, “I just don’t feel up to it. I don’t get anything out of it anymore.” She denies any thoughts of suicide but says she thinks everyone would be happier if she disappeared. She describes waking up 2 to 3 hours before the alarm clock goes off and not being able to get back to sleep. She says she lies in bed thinking about her problems over and over. Justine is otherwise healthy, except for a history of two urinary tract infections in the past 4 years. She says she had “baby blues” after the birth of her second child but was not treated. She takes no medications except for occasional ibuprofen or acetaminophen for headache or menstrual cramps. She has two children: a 14-year-old daughter and a 9-year-old son.
Depression is a common psychiatric illness. It is more serious than just feeling “down,” or having “the blues.” It is deeper and more intense than sadness or mourning, although those conditions may be the beginning of depression and share some features. Depression can be a part of other diseases, especially chronic diseases, such as Alzheimer’s and kidney failure. Sometimes depression can be caused or made worse by certain medications. Although certain groups are more likely to suffer from depression, it can affect young and old, as well as people of all genders and cultural groups. There are many treatments but no one-size-fits-all approach. Many people who have depression do not get treatment, and many self-medicate with alcohol or other drugs.
In the course of a lifetime, more than 10% of people experience depression.2 The causes of depression are not known for certain, but depressive illnesses often run in families. About 8% of patients with major depression have a close relative who has also suffered from depression. Scientists believe that the feeling of depression is due to changes in brain neurotransmitters, especially norepinephrine, serotonin, and dopamine. What causes these changes is not known, but stress, lack of sunlight and exercise, chronic disease, and poor sleep are often associated with the development of depression. The medications used in treating depression work by increasing the levels of one or all of the neurotransmitters in order to raise the mood.
The symptoms of depression are not identical in every patient. Depression is diagnosed by assessing whether a patient’s symptoms correlate with the definition of depression in the DSM-5, including number of symptoms and duration. (Depression is usually diagnosed only if a patient shows five or more signs over a period of at least 2 weeks.) All these symptoms are not necessary for a diagnosis of depression. The symptoms include pessimism and hopelessness, having much less interest and pleasure in doing usually enjoyable activities, sleeping problems (either too much or too little sleep nearly every day) often including waking up early in the morning and being unable to fall back to sleep, lack of energy, problems concentrating or making decisions, feeling worthless or excessively guilty, marked weight gain or loss, and thinking about death or suicide.1 People who are depressed often look sad or expressionless and may be either agitated and irritable or slow and sluggish. Some people with depression will say that they want to die, but many will not. Asking a person if he or she has thought about suicide does not increase the likelihood that the person will actually attempt suicide. Asking may give the opportunity to offer help.
What symptoms does Justine have that are consistent with depression? Can her depression be causing problems with her family relationships and her job?
There are many treatments for depression that do not involve drugs. Some patients will respond to a nonpharmacologic method alone. Others have found that a nonpharmacologic method in addition to medication has more benefit. The type and severity of depression varies among patients, and often different medications and nonpharmacologic treatments must be tried.
One of the nonpharmacologic approaches is talking with a psychologist, psychiatrist, or other trained therapist. The therapist uses different approaches to help the patient understand their problem, stop the pattern of negative thinking about themselves, and discover ways to overcome or manage problems and stressors. Another form of treatment for depression is intensive light exposure for several minutes a day. This method may be especially helpful for patients who have seasonal affective disorder (SAD), a form of depression that sets in during late fall and winter in response to short periods of daylight. Exercise programs help many patients who are mildly or moderately depressed. Electroconvulsive shock therapy (ECT) is beneficial for many severely depressed patients and gives improvement quicker than most other methods. A good diet may be helpful; in addition, some physicians add a “medical food,” such as methylfolate, to antidepressant regimens.
The medications used to treat depression are called antidepressants. They work to increase neurotransmitter levels by different mechanisms. (Some antidepressants are also used for other purposes, such as to treat pain conditions and to prevent migraine headaches. Antidepressants are also useful in treating anxiety, as we will discuss in the next section.) The class antidepressants is further subdivided based on how the agents work or their chemical structure. All antidepressants have one feature in common—they do not act immediately but must be taken for a few weeks to develop their full effect. Patients are often not aware of this characteristic and become discouraged with their medicine when they do not feel better right away. Patients need to be advised to give the medication a long enough trial and to check back with their doctor early in treatment to talk about their response.
The most frequently used antidepressants are the selective serotonin reuptake inhibitors (SSRIs). They have been available since the late 1980s when fluoxetine (Prozac) was released onto the market. Since then, many other SSRIs have been marketed, including paroxetine (Paxil), sertraline (Zoloft), citalopram (Celexa), fluvoxamine, and escitalopram (Lexapro). They all work by reducing the uptake of serotonin into the presynaptic nerve ending, increasing the amount of serotonin available in the synapse between two nerves (Figure 7-1).
These medicines differ in how long they last in the body and in some of their side effects. Although their actions are similar, most of them (except citalopram and escitalopram) are very different from one another chemically and it is reasonable to try a different drug in this category if the first one does not have the desired effect.
LOOK-ALIKE/SOUND-ALIKE—Care must be exercised to prevent confusing the brand name Celexa (citalopram) with other drugs like Celebrex and Cerebyx.3
Patients treated with SSRIs seldom have an immediate response. A patient will begin to have some benefit in 1 or 2 weeks after beginning the medication, but it may take 4 weeks or more to have the maximum effect. In addition, patients who need to stop taking one of these medications should taper off the medication gradually by reducing the dose over a few weeks to avoid a withdrawal syndrome that can include anxiety, sleep problems, and shock-like sensations in the arms. Paroxetine is one of the worst for the withdrawal effects, because it is quickly removed from the body. Fluoxetine has the least potential for withdrawal, because it is removed very slowly. The others are somewhere in between these two.
Justine has been prescribed Zoloft 25 mg, once daily, by her doctor. Can she expect to feel better right away?
Side effects of the SSRIs include sleep problems (less for paroxetine than the others). Many patients find that SSRI medications cause them to have trouble falling asleep. This is especially true of fluoxetine and sertraline. Dosing these medications in the morning (except for paroxetine) can help a patient avoid this problem. In addition, patients sometimes experience headaches, diarrhea, anxiety, or nausea due to SSRIs, especially when starting them. To lessen these effects, doctors will often start a patient on one-half the desired dose initially and increase to the full dosage in a few days to a week.
There is a rare but potentially dangerous side effect of SSRIs when used in combination with other medications that affect serotonin levels, called the serotonin syndrome. This syndrome can involve high or low blood pressure, confusion, diarrhea, and flushing of the skin. This is a potentially life-threatening reaction, and the patient needs to be treated in the hospital. Pharmacists monitor for other potentially interacting medications to avoid this situation.
Another class of antidepressants, the serotonin norepinephrine reuptake inhibitors (SNRIs), increases both serotonin and norepinephrine by inhibiting their reuptake. This class works similarly to the SSRIs and includes venlafaxine (Effexor XR), desvenlafaxine (Pristiq), and duloxetine (Cymbalta). This class may have a quicker onset in antidepressant effect. They are often second-line choices after the SSRIs due to side effects (especially withdrawal symptoms) and expense. The SSRIs and SNRIs are also useful in treating anxiety disorders, as we will discuss in the next section. SNRIs are often helpful in treating pain conditions, such as fibromyalgia, diabetic peripheral neuropathy, and chronic musculoskeletal pain. Some of these products (such as duloxetine) have formal indications for these conditions. Patients on SNRIs also can experience intense, distressing withdrawal symptoms when discontinuing them, or even after missing a few doses. As with the SSRIs and many other agents that act on the central nervous system (CNS), discontinuation should be gradual.
In addition to the SSRIs and SNRIs, there are medications that have additional activities. One is vilazodone (Viibryd), an SNRI that also acts as a partial agonist at one type of serotonin receptor, the 5-HT-1A receptor. Vortioxetine (Trintellix) acts as an SSRI, but has other activity at several serotonin receptors.
Selegiline, which is discussed in Chapter 6, is available as a transdermal patch (Emsam) for the treatment of depression. Another novel agent, esketamine (Spravato), is derived from ketamine (a medication used in anesthesia and, illegally, as a party drug). Esketamine is an N-methyl-D-aspartate (NMDA) antagonist (acting on some receptors that normally respond to the neurotransmitter glutamate), and is only available as a nasal spray for the treatment of depression that has not responded to other therapies. This product is administered in an office setting once or twice a week, and is only available through a restricted program. Because of a side effect called “dissociation,” which is an eerie sensation that is distressing to many patients, patients must be monitored for at least two hours after receiving the drug.4
Esketamine is intended for patient administration under the direct observation of a healthcare provider, and there is a requirement that patients are monitored by a healthcare provider for at least 2 hours. Esketamine must never be dispensed directly to a patient for home use.4
U.S. pharmacies must be certified in the SPRAVATO® REMS (Risk Evaluation and Mitigation Strategy) Program to be able to receive and dispense esketamine (a DEA Schedule III controlled substance).
Several drugs known as “atypical antipsychotics,” initially approved for the treatment of schizophrenia and other psychotic disorders (and discussed later in this chapter), have achieved approval for treatment of depression that is resistant to antidepressants alone. Some in this class are also approved for use in bipolar disorder.
When Justine returns a week later with a new prescription for Zoloft 50 mg daily, she mentions that she has been having trouble sleeping since she started the Zoloft and is looking for something over-the-counter to help her. When the technician suggests pharmacist-counseling, what might be recommended?
There are two older categories of antidepressants: the tricyclic antidepressants (TCAs) and the monoamine oxidase inhibitors (MAOIs). Both medications increase the levels of norepinephrine and serotonin in the brain, although they do this by different mechanisms. MAOIs reduce an enzyme needed for the breakdown of neurotransmitters, causing their levels to rise. Unfortunately some medicines, such as decongestants, and foods, such as aged wines and cheeses, sardines, and fermented foods, can cause dramatic increases in the levels of norepinephrine in a patient who is taking an MAOI. This can lead to very high blood pressure with risk of stroke or other adverse event. For this reason, the MAOIs, including isocarboxazid, phenelzine, and tranylcypromine, are seldom used except for treatment of patients who have not responded well to other antidepressants. Patients who take MAOIs need to be cautioned about the risks of interactions with other medications and foods.
A medication guide must be provided to the patient with each dispensing of an MAOI.
The TCAs were the main drugs used for depression for many years but have taken a back seat to newer drugs, such as the SSRIs. TCAs work by reducing the reuptake of neurotransmitters from the small space between one nerve and another, the synapse. The higher levels of neurotransmitters in the synaptic space cause a neurotransmitter effect on the connecting nerve. The result is an increase of that neurotransmitter’s activity in the brain, which improves the mood. There are many TCAs on the market. Because they have been around for so long, they are all available as generic medications, and doctors often order them using the generic name rather than the brand name. TCAs are still useful drugs for depression but have fallen from favor as first-line agents. If a patient deliberately takes an overdose of a TCA in an attempt at suicide, the TCA can cause rhythm problems in the heart, which are often fatal. The SSRIs are much safer in this regard. Since depressed patients are frequently suicidal, it is important to avoid giving them medications in amounts that can be used for a suicide attempt.
TCAs also have some other side effects that limit their use, and these side effects vary in severity from one drug to another. Anticholinergic side effects are common with the TCAs and include dry mouth, constipation, and urinary retention. Anticholinergic side effects can be especially troublesome in older patients and can even cause mental confusion. Among the TCAs, amitriptyline has the most anticholinergic activity, while desipramine has the least. Many TCAs also have some antihistamine activity, which can be useful but can also cause drowsiness. In fact, some doctors prescribe TCAs to help patients sleep. Doxepin has the most antihistamine activity of all the TCAs.
When TCAs are used to treat depression, they should be started at low doses and gradually increased over several weeks, depending on the response of the patient, side effects, and the expected effective dose of the medication. In addition to the anticholinergic side effects, TCAs can also cause orthostatic hypotension, in which the blood pressure falls when the patient gets up from a bed or chair. Patients should be advised to rise slowly from a sitting or lying position to avoid dizziness and falls.
All of the antidepressant classes discussed so far have the potential to cause sexual side effects, including decreased libido, orgasm, and erectile dysfunction. This side effect can be experienced by 20% or more of patients who use these medications, and it varies with the choice of medication and dosage. Depression itself can also cause sexual problems. Patients are often hesitant to mention sexual problems either as a symptom or a side effect. There are strategies that can be tried, and sometimes medication changes or additions will help with this problem. One class of antidepressants that does not usually cause this problem is aminoketones, of which bupropion is the only one. Bupropion (Wellbutrin) increases the levels of dopamine and norepinephrine in the brain but not serotonin levels. Bupropion is also particularly useful in treating SAD and in helping patients who wish to stop smoking. Bupropion has a less intense withdrawal syndrome than the SSRIs and SNRIs. Side effects of bupropion include sleep problems and headaches. Sometimes bupropion is added to an SSRI or SNRI if a patient is experiencing sexual problems due to the latter or to augment the antidepressant activity of another antidepressant.
When she comes to the pharmacy to get her Zoloft refill, Justine mentions that her mother told her that people on antidepressants need to avoid wine and cheese and wonders why no one told her about this. What is the likely explanation?
Trazodone (Desyrel), nefazodone, and mirtazapine (Remeron) are antidepressants that also affect neurotransmitter levels but do not fall into the categories described earlier in this section. Trazodone is more frequently used for insomnia than for depression. Mirtazapine may also help with sleep and can increase appetite and weight. It may also cause dry mouth and orthostatic hypotension. Nefazodone has many drug interactions and can cause dangerous liver damage (although this is rare). It is reserved for patients who do not respond well to other antidepressants. Both mirtazapine and nefazodone cause fewer sexual side effects than other antidepressants. (See Medication Table 7-1; Medication Tables are located at the end of the chapter.)
Victor is a 33-year-old stockbroker who, while at his doctor’s office for a routine blood pressure follow-up, mentions that he has been having spells where he feels “like the walls are closing in and I can’t escape. My gut tightens, I get sweaty, and my heart starts beating faster.” He has had this feeling for several months before meetings, but he has also started feeling this way on airplanes and trains and recently after getting stuck on an elevator for a few minutes. He has declined some work assignments that have involved travel because of these spells. When he cannot avoid travel, he has begun using rituals, such as eating the same meal before each flight, circling the gate area seven times before boarding, and carrying a worry stone in his pocket. He denies any chest pain or shortness of breath on exertion. He says that he can’t keep this up and is afraid that the problem will affect his work reviews. He says his company has been downsizing, and he is worried that he may be in the next round of layoffs. Victor is fidgeting with his keys while talking, and his fingernails show signs of chronic biting. He says he has always been a worrier “just like my dad.” Victor is unmarried, owns his home, and is healthy except for hypertension for which he takes lisinopril 20 mg daily.
Anxiety is a common factor in our lives, but it is usually not so excessive as to be considered a disorder. Anxiety can be a normal response to certain medical conditions, such as hyperthyroidism or shortness of breath. There are several anxiety disorders, including generalized anxiety disorder (GAD), post-traumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), panic, social anxiety disorder, and phobias. A patient can experience more than one anxiety disorder and often has an anxiety disorder in addition to another psychiatric diagnosis such as depression or attention deficit hyperactivity disorder (ADHD). These disorders significantly interfere with the sufferers’ lives—sometimes to the point of disability. Anxiety has been described as a feeling of fear that is disproportionate to the actual threat.4 Anxiety disorders are the most common psychiatric disorder, with more than 20% of U.S. adults having this diagnosis every year.2 Anxiety disorders are more common in women than men, often run in families, and usually develop before the age of 30.2
The reason for the development of anxiety is not well understood and probably includes several areas of the brain, including the most primitive areas, which are involved with the “fear, fight, or flight” response to a threat. Neurotransmitters believed to be involved with the anxiety response include norepinephrine, serotonin, and gamma-aminobutyric acid (GABA). GABA is the most important inhibitory (calming, suppressing) neurotransmitter in the brain. Drugs such as the benzodiazepines, which bind with GABA receptors in the brain, increase GABA activity and are one kind of medication used to treat anxiety.
The types of anxiety sound self-explanatory but deserve some elaboration. GAD is a condition in which the patient worries excessively and feels anxious most of the time. It is often accompanied by depression. OCD involves obsessions (intrusive, persistent thoughts) and compulsions (the driving need to act on those thoughts). People with OCD will ruminate on a certain idea, such as a fear of germs, and then feel compelled to try to control that fear through action, such as excessive hand washing or house cleaning. If thwarted in carrying out these compulsions, the patient will feel even more anxiety. Others will have a fear of intruders that will compel them to check the locks on their doors several times (often a specific number of times) before leaving the house. Still others will have a compulsion to pull the hairs of their eyebrows or eyelashes (trichotillomania) to ease their anxiety. Many types of OCD involve either safety or grooming issues. OCD should not be confused with obsessive-compulsive personality disorder, in which a person has a need to always be right and is excessively judgmental and controlling toward others.
PTSD is a response to a dangerous situation that the patient has experienced, such as a car wreck, house fire, rape, or battle. In addition to feelings of anxiety and depression, the patient will also often have a sleep disorder in which he or she re-experiences the traumatic event during dreaming. PTSD will sometimes appear years after the event, such as in retirement for a veteran of the battlefield.
Panic disorder is experienced as a feeling of sudden anxiety or impending doom, which can cause an overwhelming need to get out of a situation. The patient’s heart may race or pound, or the patient may have difficulty breathing or may break out in a sweat. Panic disorder can cause a person to avoid the places or situations that he or she expects to cause the panic episode. Social anxiety disorder is a fear of dealing with people or being scrutinized and judged. Both panic disorder and social anxiety disorder can lead a person to withdraw from community life, sometimes to the point of confining themself to their home (agoraphobia).
What symptoms does Victor have that suggest an anxiety disorder?
Nonpharmacologic treatment of anxiety disorders involves psychotherapy, including stress management techniques, cognitive behavioral therapy (CBT), and education on the disorder. OCD and PTSD often will not respond well to therapy alone and are among the more difficult types of anxiety to treat.
Because anxiety disorders are believed to involve the serotonin system in the brain, SSRIs and SNRIs are very useful in treating these disorders. All of the SSRI and SNRI medications can be used for anxiety disorders, although not all of them have formal Food and Drug Administration (FDA) indications for specific anxiety disorders. Clomipramine (Anafranil) is a TCA that has an FDA-approved indication for OCD. Since antidepressants can take several weeks to be effective in managing anxiety and sometimes make people feel jittery or anxious in the early phase of treatment, benzodiazepines may be used to quickly manage anxiety symptoms.5
Benzodiazepines are fast-acting medications that work by increasing the effects of GABA in the CNS. There are many benzodiazepines, which differ in onset of action, duration of action, how they are eliminated from the body, and the likelihood of interactions with other drugs. Alprazolam (Xanax) is the shortest-acting drug in this class and is usually dosed up to four times daily. Lorazepam (Ativan) is a little longer acting and is usually dosed three times a day. Diazepam (Valium) is longer acting than lorazepam and is dosed up to three times a day. Clonazepam (Klonopin) is the longest-acting drug in this class and is usually dosed once or twice a day. Other benzodiazepines—triazolam (Halcion), temazepam (Restoril), and flurazepam—are used specifically to treat insomnia. All benzodiazepines are sedating and have the potential to increase the respiratory depression caused by alcohol, barbiturates, and other sedating drugs. Patients who take benzodiazepines need to be warned that these medications can reduce alertness and make driving or operating machinery hazardous. Because benzodiazepines have the potential to become habit forming and are used illegally for recreational purposes, they are controlled substances.
Benzodiazepines have many uses beyond treating anxiety. They are used to calm an agitated or psychotic patient, relax muscle spasms, help with the management of nausea caused by chemotherapy, end seizures, manage withdrawal from alcohol and other sedating drugs of abuse, and to treat sleep disorders. Benzodiazepines used for anxiety disorders include alprazolam, diazepam, lorazepam, and clonazepam. Excessive sedation is an expected side effect, but some patients have paradoxical excitation or agitation when taking a particular benzodiazepine. In such patients, another benzodiazepine may be useful without causing that reaction. Many patients become tolerant to the sedating effects of benzodiazepines, especially after a few weeks of treatment. Diazepam and other long-acting benzodiazepines have more risk for elderly patients, especially for causing falls.
Buspirone is a medication that modifies the effects of serotonin at the serotonin 1A receptors. Buspirone affects serotonin in a manner different from the SSRIs. It is used to treat anxiety but is not habit forming and is much less sedating than the benzodiazepines. Buspirone takes 3 to 4 weeks to have its full effect in treating anxiety, so it is not useful for acute episodes. Side effects are usually mild and include dizziness, headache, and nausea. Other drugs sometimes used to treat anxiety disorders include TCAs and MAOIs, discussed in the section on depression (see Medication Table 7-2).
What medication(s) might you expect to see prescribed for Victor?
Perry is a 20-year-old man who until recently worked at a gardening store. He began working there after dropping out of the local community college, where he was enrolled for one semester. After working for about 6 months, Perry began to hear voices that told him he was no good. He also began to believe that his boss was planting small video cameras in the potted plants to catch him making mistakes. Perry became increasingly agitated at work and began talking strangely to customers (about how the other workers had it in for him and were trying to get him arrested, that he used to work for the FBI as an espionage specialist, and insisting that his name is Dirk Storm).
Perry lives with his parents. He quit his job one night after an argument with his boss about the cameras and has stayed in his room most of the time since. He will only give his parents brief comments about the people who are trying to get him in trouble. His room is a mess with clothes and food containers strewn about and several blankets covering the window. He has refused to let either parent in to help clean it up because they might interfere with a project he is working on to protect himself against people on TV who are stealing his thoughts. Perry has also neglected to bathe and frequently forgets to eat. One evening he started yelling at his mother because “she has turned against” him. His father persuaded him to take a ride in the car and took him to the hospital emergency room where he was admitted. Perry is 5’11” tall and weighs 245 lb. He denies alcohol and other drug use but smokes 1½ pack of cigarettes per day.
Schizophrenia is truly among the most tragic of medical diagnoses. Schizophrenia literally means divided mind and describes the split between the world as it really is and the way the schizophrenic patient perceives it. Schizophrenia usually develops in late adolescence or early adulthood. It occurs equally among men and women, although it often develops later in women and sometimes has a milder course. Schizophrenia affects up to 0.6% of the population in almost every culture in the world.6 It is believed to be influenced by genetic factors, and severe physical or emotional stress of the mother during pregnancy is also associated with higher incidence of schizophrenia.7 Abuse of marijuana and other drugs may also increase the risk that a person may develop a psychotic break from reality. People with schizophrenia often have abnormalities in brain structures, but exactly how these changes cause the symptoms is not known. The positive symptoms (see below) are associated with excessive activity of dopamine in the brain. There are many types of dopamine receptors in the brain, and the excessive activity at the dopamine-2 (D2) receptors are thought to drive the positive symptoms of hallucinations and delusions. Abnormalities in serotonin function are believed to influence the negative symptoms. Schizophrenia should not be confused with having multiple personalities (a dissociative disorder).
Schizophrenia often has an initial phase, when the patient is not yet diagnosed but begins to exhibit unusual behavior, such as becoming socially withdrawn, having difficulties with family members, friends, and coworkers, and becoming unusually suspicious or eccentric. The symptoms of schizophrenia are of three main types: positive symptoms, negative symptoms, and cognitive symptoms.7 Positive does not mean that the symptoms are good; it means that symptoms are present that should not be there, such as hallucinations and delusions. Delusions may be the idea that someone is persecuting the patient. This is known as paranoia. Other delusions include beliefs that someone is trying to control or steal the patient’s thoughts, beliefs that the patient is someone whom he or she is not (e.g., Moses, Jesus, Queen Elizabeth), or that simple gestures or greetings from strangers are code expressions. With schizophrenia, hallucinations are usually auditory—patients hear voices in their head, often telling them that they are evil or worthless, or telling them to do something bad or to harm themselves. Negative symptoms include a flattening in emotional response or expression, a withdrawal from social contacts, and a lack of interest in previous pleasurable activities. Cognitive symptoms include problems with memory, organization, logic, and insight into the patient’s own problem.8 People with schizophrenia are usually of normal intelligence but can have a decline in abilities as the disease progresses.
Schizophrenia is a disease that is lifelong and has no cure. It is one of the main causes of disability worldwide. Early treatment and control of symptoms is important for the long-term management of the disease, but there are many obstacles to management, including poor adherence to therapy due to poor insight into the disease or side effects of medication. Treatment of schizophrenia typically involves trials of many different medications, with relapses in which the patient has a psychotic break from reality and ends up in the hospital. People with schizophrenia are more likely to be withdrawn than to be violent but sometimes will become violent in response to their delusions and hallucinations. They are also at risk for homelessness, becoming victims of crime, substance abuse, and suicide. Interestingly, a high percentage (50% to 60%) of people with schizophrenia are also smokers, adding smoking-related illnesses to the problems faced by these patients.9
What symptoms of schizophrenia does Perry have?
Nonpharmacologic treatment can be used in addition to treatment with medication to improve the patient’s understanding of his or her disease, improve socialization, and help the patient deal with stress, substance abuse, and housing issues. Psychotherapy often includes the patient’s family, to improve understanding of the disease and family dynamics. Schizophrenia is primarily managed with medication.
Pharmacologic treatment rests most heavily on drugs called antipsychotics. Older antipsychotic drugs treat schizophrenia by blocking D2 receptors, while the newer agents (atypical antipsychotics) affect both dopamine and serotonin. Both types of antipsychotics are employed in treating schizophrenia. These drugs have been invaluable for patients with schizophrenia, helping many to normalize their lives and avoid living in institutions, but even with these medications about one-third of patients are not well managed and will have a downhill course with their disease. In addition, antipsychotics have many short- and long-term side effects that can also impair the patient’s health. Managing schizophrenia is a challenging undertaking.
Antipsychotics are categorized as typical, the older drugs that work by blocking dopamine activity, and atypical, newer drugs that antagonize (block) the serotonin 2A receptor in addition to antagonizing the D2 receptor. The atypical agents also disassociate from (let go of) the D2 receptor more quickly than the typical agents, and that is thought to reduce the risk of extrapyramidal side effects, which involve muscles and movement.8 Because of the long-term side effects of the typical antipsychotics, atypical agents are the most commonly used class now, although they have some different long-term challenges. Typical antipsychotics are further divided into low-potency and high-potency drugs, which also helps to sort out expected side effects. With low-potency drugs, higher doses are needed to provide the antipsychotic effects. Low-potency antipsychotics include chlorpromazine and thioridazine. High-potency drugs have antipsychotic activity at low doses. There are many high-potency medications on the market, including haloperidol (Haldol), fluphenazine, thiothixene, trifluoperazine, and others. Both classes have approximately equal antipsychotic activity if given at equipotent doses. For example, 300 mg of the low-potency drug chlorpromazine is equivalent to 5 mg of the high-potency drug haloperidol. This is because haloperidol is much more active at the D2 receptor than is chlorpromazine. It takes much more chlorpromazine to have the same effect as a little bit of haloperidol. Low-potency antipsychotics have more anticholinergic side effects (dry mouth, constipation, urinary retention, confusion) and cause more orthostatic hypotension than high-potency antipsychotics. Both classes can cause extrapyramidal side effects, but these side effects are more likely with low-potency antipsychotics.
When antipsychotic drugs are ordered as injections, it is important to distinguish between long-acting and immediate-acting dosage forms and dispense the correct product. Long-acting haloperidol decanoate is usually administered only once every 4 weeks (while haloperidol lactate is sometimes ordered as often as hourly) and fluphenazine decanoate is usually dosed on a 3-week schedule (while fluphenazine hydrochloride is repeated every 6 to 8 hours). Individual doses of the long-acting injections are much higher than the doses of the immediate-acting forms. Substituting an immediate-acting injection in the dose of a long-acting one can cause serious harm to the patient.
Antipsychotic drugs are available in oral dosages forms, immediate-release injectable products, and long-acting injectable (intramuscular [IM]) forms. Immediate-release injectable antipsychotics are used when a patient is agitated due to delusions and hallucinations, such as in the emergency room setting. Oral antipsychotics can be used for long-term maintenance. Long-acting injectable products called depot injections, in which the antipsychotic is added to an oil base for IM injection, are used when a patient cannot adhere to oral regimens.
Extrapyramidal side effects occur due to the effects of blocking dopamine receptors. There are several kinds of extrapyramidal reactions, but they all involve muscles and movement. Some extrapyramidal symptoms occur soon after an antipsychotic is begun, while others do not occur until after months or years of use. An early reaction that sometimes occurs is dystonia, which is a sudden, severe muscle spasm often in the neck, jaw, tongue, or eyes. Dystonic reactions usually occur within a few days of starting an antipsychotic, and it can be resolved by giving the patient an anticholinergic drug, such as benztropine, trihexyphenidyl, or diphenhydramine. Anticholinergic medications can also help with symptoms of pseudoparkinsonism, which can include slow movement, tremor, balance problems, and a mask-like face.7 Amantadine is another medication that can help with pseudoparkinsonism symptoms. Akathisia is a condition in which the patient feels restless and has the need to move in order to relieve this symptom. People with akathisia may squirm constantly when sitting, pace or tap their feet, and generally feel uncomfortable with this jittery sensation. Anticholinergics can be used for this condition also, but they do not always work. Alternative useful medications include benzodiazepines and beta blockers (such as propranolol and nadolol).
An extrapyramidal effect that is often a consequence of long-term use of typical antipsychotics is tardive dyskinesia (TD). TD is a syndrome of abnormal, involuntary body movements. It usually begins in the facial area, such as the mouth and tongue, but can include the upper body, arms, and legs. The patient will pucker, grimace, smack the lips, move the tongue around, and eventually the whole body will writhe around in a peculiar dance-like pattern. The only way to stop TD is to prevent it in the first place by monitoring the patient for abnormal movements and usually changing medications if the movements are detected.
Atypical antipsychotics cause a lower incidence of extrapyramidal side effects than the typical agents, and this is a major reason for choosing them. In addition, atypical agents are believed to help with negative symptoms, which is not the case with typical agents. Atypical antipsychotics include risperidone (Risperdal), olanzapine (Zyprexa), quetiapine (Seroquel), aripiprazole (Abilify), ziprasidone (Geodon), paliperidone (Invega), iloperidone (Fanapt), and clozapine (Clozaril). Clozapine is a special type of atypical antipsychotic. It is actually an old drug that is limited in its use due to the potential for several dangerous adverse effects, including blood cell production problems, seizures, orthostatic hypotension, and heart rhythm problems. Clozapine is still a very useful drug, especially in patients who have not responded well to other antipsychotics and in those who are suicidal, but its use must be carefully monitored with frequent blood tests to detect changes in blood cell production.
Agranulocytosis—loss of production of white blood cells (WBCs)—has been a dangerous adverse effect of clozapine therapy. WBCs are necessary to fight infection, and when their numbers are low the body can become overwhelmed by infectious agents and the patient often dies. When patients are treated with clozapine, their absolute neutrophil (a type of white blood cell) counts (ANC) must be monitored. The ANC is the combined number of both mature and immature neutrophils.
All patients who take clozapine must be recorded in a national registry of patients taking that drug to ensure that the ANC is being properly monitored. The WBC/ANC must be checked weekly for the first 6 months, every 2 weeks for the next 6 months, then monthly for as long as the patient is on the drug, if the WBC/ANC are within desirable limits. If these values are below a certain threshold, the drug must be interrupted or discontinued.10
Other side effects that may occur with antipsychotic drugs as a class include sedation, seizures, heart rhythm disturbances, blood and skin reactions, deposits in the eyes, and neuroleptic malignant syndrome—a life-threatening reaction in which the muscles become rigid and the body temperature rises dangerously. The risks of these reactions vary with the medication. Antipsychotics—including related drugs used for nausea, such as promethazine, chlorpromazine, and metoclopramide—should be avoided in patients who have Parkinson’s disease (PD). Patients with PD are already severely depleted of CNS dopamine. Using dopamine blockers such as antipsychotics will impair movement and balance. At low doses, quetiapine and clozapine have less of this effect on PD patients than the other antipsychotics.
The atypical antipsychotics have some side effects that are not usually seen in the older antipsychotics. Treatment with atypical antipsychotics is often associated with weight gain, glucose intolerance, and lipid abnormalities. These effects may lead to diabetes and cardiovascular problems. Patients who take atypical antipsychotics should be monitored for weight, waist circumference, blood glucose levels, and lipid levels. Some atypical antipsychotics, such as olanzapine and clozapine, carry a higher risk of weight gain than others (see Medication Table 7-3).
Doris is a 44-year-old woman with a 20-year history of bipolar disorder. She was brought to the emergency department of the local hospital by the police after becoming agitated and striking the assistant manager in a local restaurant. She is accompanied by her husband, Albert, who says his wife has been excitable and sleeping very little for the past 2 weeks and blamed it on the fact that last month she began stopping at the new convenience store for a large cup of coffee every day after work. She has recently started several home improvement projects and has been going on shopping sprees for expensive new clothes and jewelry and even a new car. Doris was in the hospital 3 years ago for a manic episode, which had followed several months of depression. Her moods have been controlled until now with lithium carbonate and ziprasidone. While out to dinner tonight, Doris became upset, yelling that she needed to go to Washington to help the president. While Albert and the staff were trying to calm her, she became angry and hit the manager with her purse. Albert tells the staff that he has never seen her like this, as he has only known her for 2 years. He says that he is her fourth husband and that she attempted suicide in her 20s. Doris has one daughter with depression and two uncles who are alcoholics. When she is feeling well, Doris is a peppy, friendly, and creative person, but she is prone to long bouts of depression. She works as the manager of a local theater company and drinks two to three cocktails and smokes one pack of cigarettes daily.
Bipolar disorder is a condition that affects up to 4.5% of the U.S. population.11 The exact cause is unknown, but most people with bipolar disorder have had a family member (sibling, parents, grandparents, cousins) with some psychiatric illness, including depression and substance abuse disorder, so a genetic link is strongly suggested. Bipolar disorder is characterized by mood fluctuations between depression, normal mood, and manic or hypomanic moods. A manic mood is one in which a person is extremely excited, energetic, creative, talkative, loud, distractible, and agitated. In addition, the manic patient may have wild flights of ideas, speak very rapidly and dart from subject to subject, act in an uncharacteristically promiscuous manner, spend money wildly and carelessly, and go without sleep or with little sleep for days or weeks. A manic person may also experience psychosis, including delusions of power and importance, and hallucinations. If the patient does not go all the way into out-of-control mania but still feels unusually excited, energetic, creative, or irritable, the mood is described as hypomanic, meaning less than manic.
Most patients with bipolar disorder spend the majority of their lives with either depression or normal moods, with manic and hypomanic episodes occurring infrequently. In fact, many bipolar patients are initially diagnosed with depression and may be treated for depression for years with less-than-adequate success before getting a diagnosis of bipolar disorder. Bipolar disorder is usually diagnosed between the ages of 15 and 35 and occurs in both men and women. Bipolar disorder is a major cause of disability and is also a factor in accidents, divorces, arrests, substance abuse, and suicide.
In which phase of bipolar disorder is Doris? What characteristics support this conclusion?
Bipolar disorder is primarily managed with medication, but nonpharmacologic treatments can improve the patient’s understanding of the disease and help the patient to be alert to swings into depression or mania. Psychotherapy can help with negative thinking, just as in depressed patients. Patients are also counseled to monitor their moods and sleep habits with a calendar or diary, in order to detect the beginnings of a mood change. Patients are also taught to avoid certain triggers, such as excess stress, and medications that can cause stimulation, such as decongestants and corticosteroids. In some patients, ECT is beneficial for bipolar depression.
Unfortunately, for people for whom depression can be so debilitating, the SSRI and SNRI antidepressants must be used cautiously in bipolar patients. Serotonin is believed to have an activating effect on bipolar disorder, and SSRIs and SNRIs will sometimes cause a patient in a depressed phase to switch rapidly into mania. In fact, many patients who were originally diagnosed as depressed have been shown to have bipolar disorder when treatment with an antidepressant caused a manic reaction. Many doctors recommend that patients with bipolar disorder not take SSRI or SNRI antidepressants unless they are also taking a mood stabilizer or antipsychotic drug.
The mainstay of treatment for bipolar disorder is mood stabilizers. Mood stabilizers include forms of lithium such as lithium carbonate and lithium citrate and certain antiepilepsy drugs. Among the antiepilepsy drugs, valproate, lamotrigine, and carbamazepine have been studied the most and shown effective in forms of bipolar disorder. These drugs are discussed in Chapter 6. In addition, antipsychotics, especially atypicals, are also useful in stabilizing the mood and in managing depression without promoting mania. Antipsychotics are also used to treat the acute agitation and psychosis of mania, as are benzodiazepines such as lorazepam and diazepam.
Lithium is the oldest and best-studied mood stabilizer. Lithium is a metal, similar to sodium, which exists in nature as a salt called lithium carbonate. Lithium has effects on neurotransmitters but exactly how is not known with certainty. Lithium enhances the effects of norepinephrine and serotonin in the CNS, which explains how it helps with depression, but it also has effects on the sleep cycle, body temperature, and the endocrine system. Lithium can be used to help stabilize a patient in acute mania, lifts the mood of those who are depressed, and helps to prevent the swinging from one mood to another. Some studies show that the use of lithium lowers the likelihood that a patient with bipolar disorder will commit suicide. However, lithium has several drawbacks, and therapy with this drug must be regulated by keeping blood levels within a desired range, as well as monitoring for side effects. Lithium can cause sedation, gastrointestinal side effects such as diarrhea, tremor, weight gain, and may reduce the function of the thyroid. Lithium levels can be affected by the patient’s salt and caffeine intake, dehydration, and the use of other medications, such as ibuprofen, naproxen, and diuretics.
Doris has been controlled on lithium for 2 years. Why might it suddenly have stopped working?
Of the other drugs used as mood stabilizers, valproate is especially useful for patients who cycle rapidly between depression and mania or hypomania, and lamotrigine is particularly useful in bipolar depression. Atypical antipsychotics are also useful in bipolar depression. As with patients with schizophrenia, nonadherence to treatment is common with patients with bipolar disorder. Patients often say that they enjoy the hypomanic and manic phases of their illness and feel that medications inhibit their creativity. The long-term outcome for patients with bipolar disorder is better if they can be kept stable, so that they avoid the physical and psychosocial risks associated with their mood fluctuations.
Lithium is available as two salt forms: lithium carbonate, which is used in solid dosage forms, and lithium citrate, which is available as an oral solution. Lithium citrate is labeled as 8 mEq/5 mL. Each 5 mL of lithium citrate provides the same amount of lithium that is available in the 300 mg lithium carbonate tablets. Lithium carbonate is marketed as both immediate-release (IR) products and extended-release (ER) products. Extended-release products offer less frequent dosing and may reduce gastrointestinal side effects. It is important to distinguish between the various lithium products to be sure the patient receives the dosage form and strength the physician ordered.
Attention Deficit Hyperactivity Disorder
Duncan is a 9-year-old boy repeating the second grade because of his poor progress in reading. Duncan’s mother says that he has always been “very wound up, even when he was little.” He also likes to stare out the window or open the classroom door while the teacher is giving instructions. He likes recess but has been in fights on the playground. He has trouble finishing his work and even starting it. At home, he likes to play video games and will have tantrums when told to do his homework or to go to bed. In his Sunday school class, he has often been disruptive, yelling out answers or telling stories not connected to the lesson. In the school conference about his behavior and learning problems, his dad says, “He’s just like my brother.”
The causes of ADHD are not known, but, as with many other psychiatric illnesses, genetics plays a part, with ADHD patients often having a relative with similar symptoms, even if undiagnosed. Some brain scans have shown small differences in the brain structure in patients with ADHD. Other studies suggest that patients with ADHD have a defect in the activity of dopamine and norepinephrine in the brain. ADHD affects about 5% to 10% of children in the United States, and it is more common in males than in females. More than half of these children will continue to have symptoms of ADHD into adulthood. The symptoms of ADHD revolve around problems in maintaining focus on a task. Children with ADHD are usually disorganized and easily distracted. They are often fidgety and have problems sitting still, and sometimes they are extremely energetic, as if they were propelled by a motor, darting from one brief interest to another. Some children are not as hyperactive but mostly have problems organizing and maintaining focus on their tasks. Patients who are suspected of having ADHD must display these symptoms before the age of 7 years, and in at least two areas of their lives—not just in school. In addition, children with ADHD frequently have comorbidities, which are other diagnoses, such as oppositional-defiant disorder, conduct disorder, depression, Tourette syndrome (tics), autism spectrum disorders, learning disabilities, and enuresis, which is bedwetting. Children who do not receive adequate treatment for ADHD are at risk for poor school and work performance, reckless behavior, accidents, substance abuse, and relationship problems.
What symptoms of ADHD does Duncan have? What parts of his life is this affecting?
Nonpharmacologic treatment for ADHD is centered on detecting and managing learning disorders and giving the child a structured environment with clear rules, with incentives and rewards for good performance. Nonpharmacologic treatment by itself is usually not adequate for managing the attention problems associated with ADHD, but it is beneficial when used along with medication.
Pharmacologic management of ADHD centers on CNS stimulants. In addition, other medications are also used, including antidepressants, antipsychotics, mood stabilizers, and certain medicines originally used to control blood pressure, such as clonidine and guanfacine. It often takes trial and error to find the optimal medication for a child or adult with ADHD. Doctors will usually focus on the most distressing or problematic symptoms and aim medication at controlling those symptoms.
The drug of choice for patients with ADHD is one of the CNS stimulants. Stimulants enhance the effects of norepinephrine and dopamine in the CNS, improving the ability to focus and tune out distractions. (In a weaker manner, this function is also accomplished by caffeine and nicotine use.) Either methylphenidate or an amphetamine compound is used as the first choice. All of the stimulant medications are variations methylphenidate and amphetamines. Some of the variations are chemical—such as dexmethylphenidate and dextroamphetamine—and others are variations in the dosage form—such as several types of sustained action preparations and transdermal patches. The particular choice usually depends on patient factors (such as age of the patient), whether the patient’s schedule will allow for drug administration, and prescriber preference. If the patient does not do well with the first stimulant choice, due to less-than-optimal response or side effects, another stimulant is chosen. Side effects of stimulants include jitteriness, sleep disturbances, loss of appetite, gastrointestinal upset, tics, and possible increases in heart rate and blood pressure. To reduce side effects, doses should begin low and be titrated to the most effective and tolerated dosage.
Children are often unable or unwilling to take solid tablets and capsules, so parents should inquire about options that are easier to administer. Only immediate-release tablet forms (Ritalin, Adderall) may be crushed and mixed with food for administration. Only scored tablets may be cut in half. Some extended-release capsules, including Adderall XR and Aptensio XRs, may be opened and sprinkled on applesauce for children who cannot swallow the intact capsule. Vyvanse capsules may be opened and mixed with water, yogurt, or orange juice. It is important to consult product literature for information on proper and safe administration of each product, as there are many differences between them.
The various stimulant products are designed to meet the focus, duration, and tolerance needs of the patient. Immediate-release products work quickly but must be dosed both in the morning and in the middle of the day to provide coverage throughout the school or work day. Extended-release products take longer to start working in the morning but have sustained activity throughout the day. Some products, such as Aptensio XR, Ritalin LA, Focalin XR (dexmethylphenidate), and Adderall XR (a mixture of amphetamine and dextroamphetamine), combine both immediate-release and extended-release forms of the stimulant drug. Methylphenidate patches (Daytrana) also provide sustained activity. The patches are worn for 9 hours and provide therapeutic activity for 12 hours. Vyvanse (lisdexamfetamine) is a prodrug that is converted in the body to dexamphetamine. It, too, has sustained activity and is dosed once daily in the morning. Jornay PM is an extended-release methylphenidate product that is dosed in the evening but is delayed in its action until the following day.
All stimulants currently available in the United States for the treatment of ADHD are Drug Enforcement Administration (DEA) Schedule II controlled substances. Prescriptions for them are subject to all the rules for such medications and can never be refilled or renewed via telephone.
If the stimulant class does not benefit the patient or is not tolerated, drugs from the antidepressant class are tried. Other reasons for choosing this class is if the patient is also depressed or if someone in the patient’s household abuses drugs. Drugs in this class—bupropion; the tricyclic antidepressants imipramine, desipramine, and nortriptyline; and atomoxetine—also enhance the effects of norepinephrine and dopamine in the CNS by mechanisms different than those of the stimulants. Atomoxetine is a selective norepinephrine reuptake inhibitor, which was specifically approved by the FDA for the treatment of ADHD.12 Side effects are similar to those of the stimulants, although this class usually has less effect on sleep.
While Duncan’s mother understands that he will not become addicted to stimulant medications, she is uncomfortable with having controlled substances in her home. She is also concerned that she may be unable to travel to Duncan’s physician’s office every month for a new prescription. What are some other options for his treatment?
Clonidine and guanfacine are alpha-2 adrenergic agonists. They were originally developed to treat high blood pressure, but they have the effect in the CNS to improve blood flow to the prefrontal cortex, which is the “thinking” part of the brain behind the forehead. The effect is to enhance memory and decision making. These drugs also have effects on norepinephrine activity. Both clonidine and guanfacine can be used alone for ADHD but are more commonly used as adjuncts to stimulants to improve sleep and to reduce disruptive behavior.5 Clonidine and guanfacine can cause sedation, dry mouth, dizziness, reduced blood pressure, and constipation. These drugs are especially useful in patients with ADHD who also have Tourette syndrome, since they also help to control tics.
Antipsychotics, especially atypical agents, are also employed to treat ADHD. As with clonidine and guanfacine, they are also useful in treating comorbid Tourette syndrome. In addition, antipsychotics and mood stabilizers help with aggressive behavior and conduct disorder (see Medication Table 7-4).
Substance Use Disorders
Joel is a 26-year-old man who has been arrested for public intoxication after a football game. Joel had a previous arrest 3 years ago for trying to pass an altered prescription. He started drinking beer and smoking marijuana at a friend’s house in the ninth grade. While Joel had been a good student in middle school, he barely managed to graduate from high school. His mother admitted him to a teen rehabilitation program during his senior year. He stayed off alcohol and drugs for 18 months but has had several relapses since. He was admitted to the hospital 1 year ago for pancreatitis due to excessive alcohol use. After this arrest, Joel was taken to the hospital for detoxification. His toxicology screen tested positive for alcohol, hydrocodone, and cocaine.
Substance use disorder is a problem an individual experiences that has serious consequences for families and communities—even internationally. It is a common comorbidity in patients with other psychiatric disorders and is a cause of crime, broken relationships, physical ailments, and child neglect. Substance use disorder can be relatively mild, such as the jitteriness that comes from overuse of coffee and other caffeinated drinks, or deadly, due to respiratory depression from opioid or other overdoses or seizures and heart rhythm problems due to cocaine. Alcohol use disorder alone is a cause of liver disease, pancreatitis (inflammation of the pancreas), cognitive decline, cancer, homelessness, and disabling and fatal accidents. While the use of some substances such as tobacco mostly affects the user and his or her family, the use of others, such as methamphetamine, are a major societal problem. Each year, the United States spends more than $400 billion on problems related to substance use disorders, which are the biggest preventable source of illness, death, and disability in the country.13
Substance use disorder is a maladaptive use of a drug with repeated negative consequences to the user due to that use. It is important to remember that many drugs implicated in substance use disorders are also legal medications with legitimate uses.
Addiction refers to a chronic, compulsive craving of a drug, which will cause a person to lose control of his or her behavior and use the drug in spite of the consequences. In contrast, a patient may become tolerant to the therapeutic effects or side effects of a drug, meaning that the dose would need to be increased to give the same effect. Physical dependence means that a patient may experience withdrawal symptoms if a drug is suddenly stopped. Tolerance and physical dependence are normal conditions that develop with many drugs. Merely experiencing tolerance or physical dependence does not make a person addicted to a drug. For example, a patient with cancer or some other debilitating painful disease may need high doses of opioids in addition to benzodiazepines for anxiety or muscle spasms. The patient is not considered to have a substance use disorder, but a person who steals those same medications to use them recreationally is. Similarly, many drugs, such as antidepressants, beta blockers, proton pump inhibitors, and antiepileptics, can cause physical dependence or tolerance; however, these patients are not addicted because they are using the medications for legitimate purposes, under supervision, and without the craving, compulsive drive associated with addiction. Drugs used by people with substance use disorders have many effects on the CNS. Depending on the drug, it may cause stimulation (as with cocaine and methamphetamine), sedation (as with benzodiazepines, barbiturates, alcohol, and marijuana), or some other effect (such as the hallucinations associated with LSD). Some non-drug products (eg, inhalants [spray paint], airplane glue, dry erase markers) are used by individuals with substance use disorders. Even some OTC medications, such as pseudoephedrine and dextromethorphan, have abuse potential. The withdrawal pattern with these medications varies with the drug, dosage, length of time it has been taken, and patient individual factors.
We must also be careful of the terms we use in describing the use of drugs with abuse potential, distinguishing addiction from tolerance and dependence.
Which of Joel’s characteristics are consistent with substance use disorder?
The nonpharmacologic treatment of substance use disorder includes individual psychotherapy and 12-step support groups, such as Alcoholics Anonymous. There are many inpatient and outpatient programs that specialize in the treatment of substance use disorders. Relapses are common though, and it often takes many attempts over several years before a person manages to recover from substance use disorder.
Not all abused substances are physically habit forming or addictive. Substances such as marijuana, inhalants, and hallucinogens are often psychologically habit forming, but there is little or no withdrawal syndrome when their use is abruptly stopped. This section will focus on those physically addictive drugs for which there are medicinal approaches to manage dependency and withdrawal (see Medication Table 7-5). There are two main goals of managing substance use disorder: 1) managing the acute withdrawal symptoms and avoiding the consequences of acute withdrawal (such as seizures, agitation, and sleep disturbances in withdrawal from alcohol and other sedatives), and 2) managing the craving and compulsive desire for the drug in the long term.
For nicotine users, the most intense phase of withdrawal is in the first hours, days, and weeks. Nicotine has an intense but brief effect, and withdrawal from it is also intense and usually brief although the habits accompanying smoking—smoking when eating, smoking when with smokers, smoking when driving—and the craving for nicotine can take months or even years to dissipate. Patients who are withdrawing from nicotine experience a physical withdrawal, such as feeling tired, anxious, agitated, less mentally focused, and constipated. The physical withdrawal intensity is closely related to the daily intake of nicotine. There are two approaches to managing nicotine withdrawal. For nicotine replacement therapy, gums (Nicorette), patches (Nicoderm CQ), lozenges (Commit), nasal sprays (Nicotrol NS), or nasal inhalers (Nicotrol inhaler) containing nicotine are used to manage the acute withdrawal and then gradually tapered off. Oral medications, bupropion (Wellbutrin) and varenicline may manage the withdrawal symptoms by actions on neurotransmitter activity in the CNS. Nicotine gums, patches, and lozenges are available over the counter (OTC). A prescription is required for Nicotrol inhaler and Nicotrol NS (nasal spray), as well as bupropion and varenicline.
Bupropion is indicated and prescribed for psychiatric disorders as well as for smoking cessation and has specific dosage ranges depending on its use. This may affect insurance coverage. Most plans, for instance, cover bupropion for depression but may not cover bupropion for smoking cessation. Some plans require prior authorization before filling a prescription for bupropion, so that only prescriptions used for depression are covered.
With alcohol withdrawal, the acute phase bears the risk of seizures due to the sudden decrease in the sedating power of alcohol. In addition, patients with alcohol use disorder are often deficient in vitamins, especially thiamine, which is necessary for good functioning of the CNS. The management of alcohol withdrawal focuses on replacing vitamins and replacing the sedative effects of alcohol by using a benzodiazepine, such as diazepam or lorazepam, and then gradually withdrawing the benzodiazepine. After the acute withdrawal, the goal is to prevent the patient from relapsing. This can be aided medically by using disulfiram (sometimes still called by its former brand name, Antabuse), naltrexone (Vivitrol), or acamprosate. They work by entirely different mechanisms. Disulfiram tablets cause intense nausea and vomiting, headaches, and flushing when someone drinks alcohol while taking this medicine. This is a negative feedback to discourage alcohol use. The reaction to disulfiram can also cause seizures and serious cardiac effects, so this drug should not be used in patients already at risk of these events.
In nicotine replacement therapy, the smokers’ smoking habits and total daily intake of nicotine are used to determine the initial dose that will reduce cravings for nicotine and the urge to smoke. Over the next several weeks, patients reduce the amount of gum or the dosage of the patch until they are off the medication all together. With bupropion and varenicline, patients set a date to stop smoking a couple of weeks away, start the medication at a low dosage, taper up to the effective dose, and then stop smoking on the set date. By that time, the medication has sufficient levels in the CNS to replace the effects of nicotine in the brain. These medications take away the reward for smoking so that patients do not have as much interest in the activity. The side effects of bupropion were discussed earlier. Varenicline can cause sleeping problems, including insomnia and disturbing dreams. Nausea, dry mouth, and headaches are also common side effects. Patients who experience depression, suicidal thoughts, or changes in behavior while taking varenicline should stop taking the drug immediately and consult their doctors.14
Patients taking disulfiram must be warned to avoid all alcohol, including that found in cough medicines, sauces, and even skin products such as aftershave lotions. A serious reaction to alcohol can occur up to 14 days after disulfiram is discontinued.
Naltrexone and acamprosate reduce the cravings for alcohol. Both medications commonly cause nausea.14
Opioid withdrawal can be managed with supportive therapy during the early phase, which is not life-threatening but can cause intense muscle cramping, gastrointestinal distress, and agitation. Many opioid-addicted patients benefit from enrollment in a methadone maintenance program. Methadone is an opioid that has a very long duration in the body. The peak effect does not give the intense high of shorter-acting opioids, and the cravings are suppressed by the long-acting effects of methadone. This program does replace one dependency with another but allows the patient to return to a productive place in society while learning to manage life without opioids. When methadone is used to manage opioid addiction, it must be done in a licensed methadone clinic according to federal law. (Methadone used to treat pain does not have this requirement.)
LOOK-ALIKE/SOUND-ALIKE—Psychiatric medications involved in look-alike/sound-alike errors include alprazolam and lorazepam (both for anxiety); Celexa (citalopram, depression) and Celebrex (celecoxib, arthritis); Klonopin (clonazepam, seizures) and clonidine (ADHD, hypertension); clozapine (for schizophrenia) and trazodone (sleep, depression) and tramadol (pain).
Another option for managing patients who wish to stop abusing opioids is to employ buprenorphine, a drug that both has some of the effects of opioids and blocks other effects. Two drugs containing buprenorphine are used in an acute and long-term manner to reduce the drug-craving urges of the patient. Buprenorphine alone is used at the beginning of treatment, when the patient’s withdrawal symptoms are most intense. Later, a combination buprenorphine/naloxone sublingual or buccal preparation (Suboxone, Zubsolv) is used in the maintenance phase of management. Naloxone, a narcotic antagonist (discussed in detail in chapter 5), is added to buprenorphine to block the effects of buprenorphine if the user tries to dissolve and inject the drug. Doctors who prescribe buprenorphine preparations for substance abuse must have the proper credentials and be trained in the use of these products.
LOOK-ALIKE/SOUND-ALIKE: Buprenorphine has been confused with hydromorphone.3
Like naloxone, naltrexone blocks the effects of opioids, but it is not used to counteract acute opioid overdoses, as naloxone is. Naltrexone is used in a 50 mg daily oral dose and a 380 mg once monthly intramuscular injection (Vivitrol) to block the effects of opioids and assist the maintenance of sobriety. As mentioned earlier, naltrexone is also used to reduce the urge to drink alcohol.
Because psychiatric disorders are often expressed by behavioral rather than physical signs, patients suffering from them are sometimes incorrectly considered to be at fault for their own symptoms and judged in a negative manner. It is important for the pharmacy technician to remember that these conditions, across the spectrum from depression and psychosis, through attention deficit hyperactivity disorder (ADHD) and substance use disorders, are real illnesses and that patients receiving treatment for them deserve just as much consideration and care as is extended to those who have asthma or heart disease. Many of the medications used in the therapy of psychiatric disorders affect the neurotransmitters detailed in Chapter 4 and Chapter 5 and have side effects often throughout the body related to the actions of these neurological messengers. Some patients have short-term therapy, but many must be treated for a lifetime for conditions that can only be controlled and not cured.
MeltonST, KirkwoodCK. Anxiety disorders: Generalized anxiety, panic, and social anxiety disorders. In: DiPiroJT, YeeGC, PoseyL, et al., eds. Pharmacotherapy: A Pathophysiologic Approach. 11th ed. New York, NY: McGraw Hill; 2020.
MeltonST, KirkwoodCK. Anxiety disorders: Generalized anxiety, panic, and social anxiety disorders. In: DiPiroJT, YeeGC, PoseyL, et al., eds. Pharmacotherapy: A Pathophysiologic Approach. 11th ed. New York, NY: McGraw Hill; 2020.)| false
U.S. Department of Health and Human Services, Office of the Surgeon General.Facing Addiction in America: The Surgeon General’s Report on Alcohol, Drugs, and Health. Washington, DC: U.S. Department of Health and Human Services; 2016.
U.S. Department of Health and Human Services, Office of the Surgeon General. Facing Addiction in America: The Surgeon General’s Report on Alcohol, Drugs, and Health. Washington, DC: U.S. Department of Health and Human Services; 2016.)| false