The Pharmacist's Role in Mental Health
Kathy Hitchens, Drug Topics
The newspaper headlines scream "not guilty by reason of insanity" for a criminal on trial. The hot gossip around the office concerns who is taking antidepressants. And the word on the talk shows is that millions of dollars are spent on legal as well as illegal psychoactive drugs every year. How relevant is mental illness to the practicing pharmacist? The short answer: Very. Considering the incidence of mental illness, the therapeutic concerns in pharmacotherapy, the problems of patient compliance, the importance of the pharmacist's expertise in drug therapy, and the pharmacy's presence in almost every neighborhood, R.Ph.s have the potential to play a vital role in assisting people with mental illness.
The estimated incidence of mental illness in the United States in the community setting is significant. According to the Epidemiologic Catchment Area study, 28% of adults had an active mental or addictive disorder in the past year and another 16% had a disorder at some time prior to the past year. Thus, the estimated prevalence of mental disorders in the lifetime of adults living in the United States approaches 44%. If this seems hard to believe, bear in mind that only one-third of disorders have associated impairment and many disorders are of relatively short duration. Even looking at the statistics conservatively, it's a safe bet that a good number of adults affected by mental illness pass through the doors of the community pharmacy.
The prevalence of specific types of mental illnesses varies. As a group, anxiety disorders, including phobia, panic disorder, and obsessive-compulsive disorder, are the most prevalent mental conditions. Approximately 13% of people had active symptoms of anxiety disorders during the preceding year. Next in prevalence are affective disorders (primarily depression) and substance-abuse disorders (primarily alcohol-use disorder). Schizophrenic disorder, somatization disorder, and antisocial personality disorder have a smaller incidence.
Although community pharmacists will encounter patients with undiagnosed mental disorders, most often the pharmacist's role in the community pharmacy will be to assist a patient who has been diagnosed with mental illness with the prescribed therapeutic regimen. Still, the diagnosis is the logical starting point in boning up on mental illness. Diagnosis of mental illness
Diagnosis of mental illness differs from most other medical diagnoses because lab tests, X-rays, and scans do not apply to psychiatric illness. A diagnosis is based primarily on phenomenology-that is, the descriptive symptoms of the syndrome of interest. Clinicians use criteria such as the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), to categorize symptoms into a diagnosis.
The DSM-IV contains a wealth of information on all mental disorders recognized by the American Psychiatric Association. In addition to the DSM-IV rating scales, such as the Hamilton Scale for Depression, the Hamilton Scale for Anxiety, and the Clinical Global Impression Scale, a multitude of others are used to provide objective data about mental illness and to answer clinical or research questions. Rating scales used repeatedly over a period of time can be used to monitor change during treatment.
Even with the established criteria, mental illness diagnosis is not always straightforward. Many factors cloud the picture. First, psychiatric diagnosis can be comorbid with other clinical psychiatric disorders. For example, during their lifetime, more than 40% of patients with major depressive disorder meet criteria for one or more nonmood psychiatric disorders. As one mi ht guess, comorbid conditions often make treatment more complex because a coexisting disorder may change the course of the illness and/or alter treatment response. Second, mental illness may also be comorbid with medical illness.
The subjective nature of diagnosis, treatment, and monitoring of psychiatric illness underscores the need of a patient for professional assistance. Because the quality, capabilities, and costs vary widely among mental health-care providers, the starting point for diagnosis and treatment is usually to investigate the available options. Local mental health organizations and rehabilitative services are listed in the Yellow Pages. Another possible resource is the nearby hospital; many hospitals assist patients in health-care referral, including mental health services. In addition, crisis hotlines exist in many parts of the country to aid the public in dealing with mental health emergencies.
Diagnosis and treatment of mental illness occur in a variety of settings. The percentage of patients with mental illness and addictive disorders treated by specialists in the mental health sector is approximately equal to the percentage treated by clinicians in the general medical care sector. A lesser percentage of patients are treated by other human service professionals (clergy, social service agencies) or turn to a network of support groups (self-help, family, and friends). Drug therapy in mental illness
Once mental illness is diagnosed, appropriate therapy is planned by the mental health clinician. Therapy may include medication, training in behavior modification, psychotherapy, or a combination of all three. Therapy, including pharmacotherapy, is tailored to the diagnosis and symptoms. However, a close investigation of DSM-IV shows that many forms of mental illness have overlapping symptoms. As most community pharmacists are not privy to any diagnosis, let alone a detailed diagnosis, it is most practical to consider drug therapy according to drug categories rather than diagnoses. In this article, psychoactive drugs are grouped as anxiolytics, antidepressants, mood stabilizers, and antipsychotics. Anxiolytic drugs
One of the mainstays of psychopharmacotherapy is the use of anxiolytic drugs. Commonly used anxiolytics include benzodiazepines and buspirone. Benzodiazepines are used to manage clinically significant anxiety and agitation in a variety of situations, including generalized anxiety disorder, phobias, panic disorder, and depression. They are useful both in brief courses for acute transient stressors and in a consistent regimen for DSM-IV anxiety disorders. The number of available benzodiazepines allows prescribers to choose among a range of drug potencies, pharmacokinetic parameters, and metabolism. Approximate equipotency of benzodiazepines is shown in Table 1.
Diazepam and clorazepate have the most rapid absorption (and consequently onset) of the oral benzodiazepines (30-60 minutes), while oxazepam and prazepam have the slowest absorption (onset). With a half-life of 36-96 hours, clorazepate, halazepam, and prazepam have the longest duration of action. Oxazepam has the shortest half-life: five to 15 hours.
Short-term adverse effects of benzodiazepines include sedation, fatigue, ataxia, slurred speech, amnesia, and impaired cognitive function and motor skills. When side effects are severe or impair daily activities, dosage may need to be adjusted to a lower level. Patients who persistently request increased doses of benzodiazepines may be having problems with comorbid substance abuse.
Benzodiazepines interact with central nervous system (CNS) depressants to potentiate sedative effects. Alcohol consumed with benzodiazepines increases the sedation and psychomotor effects. While an overdose of benzodiazepines alone is rarely life-threatening in combination with alcohol or other CNS depressants, an overdose can be fatal.
Antacids decrease the rate and extent of clorazepate absorption. Cimetidine prolongs the half-life of single doses of diazepam, chlordiazepoxide, and alprazolam, which are metabolized through the hepatic cytochrome P-450 enzyme system. However, at least one study has demonstrated that the effect of adding cimetidine to diazepam therapy is not clinically significant in healthy patients on long-term therapy. In an elderly or debilitated patient on chronic benzodiazepine therapy receiving cimetidine, the preferred choices are lorazepam or oxazepam because they are metabolized by conjugation and, consequently, are unaffected by cimetidine.
Benzodiazepine metabolism is impaired by theophylline, disulfiram, fluoxetine, isoniazid, omeprazole, rifampin, and low-dose estrogens. Alprazolam levels are increased by 100% by the addition of nefazodone and fluvoxamine; for this reason, the alprazolam dose should be decreased by 50% when these drugs are added to the regimen.
Despite the potential for dependence and abuse, studies have shown that diazepam treatment and clorazepate treatment of six months' duration benefit patients with generalized anxiety disorders. Alprazolam treatment for as long as eight months has been beneficial to patients who have panic disorder. Many experts believe the best way to determine the need for continued medication is to periodically discontinue the medicine and reassess its need, based on the patient's response.
Risk for rebound (prompt, brief recurrence of symptoms after sudden discontinuation of medicine) or withdrawal syndrome (development of more persistent anxiety symptoms than were originally present) is increased in anxious patients treated with benzodiazepines for four months or longer. Mild withdrawal symptoms have also been reported in up to 44% of patients taking therapeutic doses for four to six weeks.
To minimize the risk of rebound and withdrawal symptoms, benzodiazepines should be discontinued gradually after extended use. Sometimes in the course of tapering dosage, benzodiazepines with a longer half-life are substituted for those with a shorter half-life, to minimize the severity of symptoms.
Buspirone differs from the benzodiazepines in structure and pharmacology. It does not have side effects of sedation, psychomotor impairment, dependence, withdrawal syndrome, or abuse potential associated with benzodiazepines, nor does it interact with alcohol. Buspirone has been used successfully to treat generalized anxiety disorder, especially with associated depressive symptoms. However, full therapeutic effectiveness of buspirone is delayed for several weeks; thus, it is used in patients experiencing chronic anxiety rather than acute stresses. Adverse effects of buspirone include nausea, dizziness, headaches, and fatigue.
So how does the community pharmacist help the anxious patient? Pharmacists assist anxious patients by educating them about the drug therapy, the common side effects of their medicine, and how to deal with these side effects. Pharmacists can warn about potential interactions with over-thecounter products. Naturally, pharmacists always monitor drug therapy for drug interactions and counsel the patient or call the physician to make changes when appropriate. Importantly, pharmacists can explain restrictions that occur on refills of scheduled drugs, so the anxious patient isn't drumming his fingers on the counter while the pharmacist tries to phone the doctor. Antidepressants
Antidepressants compose a significant part of the psychotherapeutic therapy armamentarium. Originally used almost exclusively to treat depression, some antidepressants now have approved indications that include obsessive-compulsive disorder and bulimia nervosa. Antidepressants are used in a variety of other conditions as well, including panic disorder, post-traumatic stress disorder, and social phobia. Monoamine oxidase inhibitors
The monoamine oxidase inhibitors (MAOIs) were the pioneers of antidepressants. (Phenelzine and tranylcypromine are the only two MAOIs approved in the United States for use in depression.) Though effective in treating depression, enthusiasm for these drugs waned after 1963, when reports of potentially fatal interactions between MAOlrs and foods containing tyramine emerged. However, appropriate dietary restrictions minimize the risk of hypertensive crises with MAOIs. But, at one time, the list of forbidden agents with MAOIs swelled to 70 different foods and beverages. Studies such as one published by Gardner et al. in the Journal of Clinical Psychiatry (March 1996;57:99-104) have revised the list and determined many "blacklisted" foods are safe. The traditional MAOI-diet restrictions still exist: aged cheeses, aged and cured meats, banana peel, broad-bean pods, Marmite, sauerkraut, meat or poultry or fish that has been improperly stored or spoiled, soy sauce and other soybean condiments, and tap beer. The list by Gardner et al. is more lenient, categorizing red or white wine and bottled or canned beer (including nonalcoholic varieties) as moderately restricted foods.
Food restrictions notwithstanding, MAOIs still have interactions with other drugs, which are important to consider (Table 2). The most frequent adverse effect of MAOIs is postural hypotension, which is more significant with phenelzine than with tranylcypromine. A divided-dose schedule minimizes the likelihood of hypotensive reaction. Although anticholinergic effects are common with MAOIs (especially dry mouth and constipation), the effect is milder than that associated with tricyclic antidepressants (TCAs).
Phenelzine is associated with mild-to-moderate sedating effects, while tranylcypromine may cause stimulation. For this reason, the last dose of tranylcypromine should be administered in the early afternoon. Tricylic antidepressants (TCAs)
Shortly after the first MAOI was approved, the first TCA, imipramine, reached the market. Although highly effective in treating depression, the incidence of anticholinergic effects reduced patient compliance with therapy. Newer TCAs have less significant anticholinergic effects and probably better patient compliance with therapy. The intensity of sedative effects, hypotensive effects, and anticholinergic effects are shown in Table 3.
Patients treated with TCAs are usually started on a low dose that may be increased every three days until therapeutic levels are reached. The relationship between plasma concentrations and dosage levels varies widely among patients; thus, patients are not considered refractory to tricyclics without blood-level monitoring.
Anticholinergic side effects most frequently associated with TCAs (dry mouth, constipation, blurred vision, urinary retention, dizziness, tachycardia, and memory impairment) impact patient tolerance and compliance, particularly in the elderly and in patients receiving long-term therapy. The risk of syncope caused by orthostatic hypotension can increase the risk of falls in elderly patients.
TCAs can also cause cardiovascular effects: cardiac conduction delays, heart block in patients with preexisting conduction disease, and severe arrhythmias in patients who overdose. Discontinuing therapy abruptly (especially when daily dose exceeds 300 mg) is associated with dizziness, nausea, diarrhea, insomnia, and restlessness.
TCA therapy is affected by a multitude of factors including the following: changes in physiology, genetics, age, cigarette smoking, and hepatic disease. TCAs are metabolized by the liver; thus, they interact with drugs that modify the cytochrome P-450 hepatic enzyme system or drugs that modify the hepatic blood flow. They are also extensively protein-bound, so they may cause interactions by displacing other drugs from protein-binding sites. See Table 4. Selective serotonin reuptake inhibitors (SSRIs) The first selective SSRI, fluoxetine, was approved in 1988. Since then, sertraline and paroxetine have been added to the SSRI family. Evidence to date suggests the SSRIs are equivalent to the TCAs in the treatment of depression. Another SSRI, fluvoxamine, has also been approved in the United States, but its current approved indication is obsessive-compulsive disorder.
SSRIs have fewer anticholinergic and cardiovascular side effects than TCAs and are not associated with weight gain. The main adverse events (which are generally mild and short term) include gastrointestinal symptoms of nausea, vomiting, or diarrhea; and sexual dysfunction in both males and females. Headache, insomnia, and fatigue are also reported. SSRIs as a group improve anxiety symptoms that accompany depression. However, sometimes patients, particularly those taking fluoxetine, notice increased anxiety early in treatment. Anxiety, if it occurs, is generally mild, occurs early in treatment, and is short-lived.
SSRIs, venlafaxine, and nefazodone inhibit enzymes of the cytochrome P-45Q system. Clinicians are still sorting out the significance of drug interactions predicted by this enzyme inhibition. Table 5 lists P-450 enzymes and the drugs they affect.
Psychotropic-SSRI drug interactions known to be clinically important include those that can trigger "serotonin syndrome." Symptoms include confusion, sweating, fever, rigidity, tachycardia, hypotension, and, if severe, possibly death. The serotonin syndrome has been reported in patients receiving an MAOI who take an SSRI or tryptophan. To prevent the serotonin syndrome, a patient who is switched from an SSRI to a MAOI must have a twoweek washout period between drugs. (Patients taking fluoxetine should have a five-week washout period.) Patients who are switched from an MAOI to an SSRI require a two-week washout for an irreversible MAOI.
Patients receiving SSRIs and tryptophan, or SSRIs and lithium, sometimes experience a milder serotonin-like effect characterized by increased rigidity, myoclonus, agitation, or mild elevations in vital signs.
TCAs and SSRIs interact because SSRIs inhibit cytochrome P-450 enzymes that metabolize TCAs. Nevertheless, the combination of an SSRI with a low dose of a TCA appears to be gaining clinical acceptance as therapy for nonresponders.
SSRIs are used for patients who have residual depression symptoms and along with neuroleptics in the treatment of psychotic depression. As fluoxetine and paroxetine particularly inhibit the CYP2D6, neuroleptic clearance may be reduced. Therefore, these patients have an increased risk of extrapyramidal symptoms (EPS).
To be effective, trazodone and nefazodone require divided dosing. Both have minimal anticholinergic effects but can cause orthostatic hypotension. Trazodone's common side effects include sedation and cognitive slowing. Nefazodone's common side effects include light-headedness, dizziness, sleepiness, dry mouth, nausea, and weakness.
Bupropion is an effective antidepressant that causes few cardiovascular effects and little sedation or sexual dysfunction. However, bupropion can cause seizures that are dose-related, so a single dose should not exceed 150 mg and the daily dose should not exceed 450 mg. Other side effects of bupropion include dry mouth, constipation, headache, insomnia, agitation, nausea, and weight loss.
Venlafaxine, a relatively new addition to antidepressant therapy, is structurally different from other antidepressants. The most commonly reported adverse events associated with venlafaxine include nausea, constipation, somnolence, dry mouth, dizziness, nervousness, sweating, asthenia, abnormal ejaculation/orgasm, and anorexia. Venlafaxine can cause a dose-related increase in blood pressure; therefore, blood pressure should be monitored throughout therapy.
Mirtazapine is the newest addition to the antidepressant therapy options. Because agranulocytosis is a possible side effect, patients should be advised to contact their physician if fever, chills, sore throat, mucous membrane ulceration, or other signs of infection develop. The most commonly reported adverse events are nausea, somnolence, increased appetite, weight gain, and dizziness. Although patients may notice improvement in symptoms in one to four weeks, they should continue therapy for the full recommended time. Mirtazapine can impair cognitive and motor skills, so patients should be cautioned about driving a vehicle or operating dangerous machinery, and advised not to drink alcohol while taking mirtazapine.
The possibility that antidepressants can cause birth defects has been a subject of repeated speculation. However, numerous well-documented studies have found tricyclic antidepressants and SSRIs to be safe treatment options in pregnancy. Although recent concerns have surfaced about a link between fluoxetine and perinatal complications, the study has been criticized for using inappropriate design. In pregnancy, antidepression therapylike other therapies-should be taken only when the risks to the mother and baby of no treatment outweigh the risks of treatment.
The American Academy of Pediatrics does not discourage breast-feeding in mothers taking antidepressants; however, the effects of TCAs, SSRIs, and bupropion on the nursing infant are unknown and may be of concern.
How does the pharmacist help the patient taking an antidepressant? First, by not jumping to the conclusion that the patient taking an antidepressant has symptoms of depression. Many antidepressants have different approved indications. For the patient who is depressed, a pharmacist needs to recognize how depression affects a patient's ability to concentrate, rate of thinking, and memory of recent events. Consequently, the more severe the depression, the more difficulty the patient will have following directions or retaining information. Providing the patient with simple, basic information at the onset of treatment-perhaps in written format-will be helpful. As depression improves, the patient can be given additional information. If the patient displays suicidal tendencies, either in conversation or behavior (such as attempting to fill prescriptions in quantity), it is important to contact the physician as soon as possible. Patients must be educated about the importance of completing therapy to minimize the likelihood of recurrence. Pharmacists can also help patients taking antidepressants by monitoring drug interactions and medications that can cause depression and by intervening if necessary to improve drug therapy.
Mood stabilizers are used to treat mania. In 70% to 80% of patients with bipolar disorder, lithium is effective in preventing acute mania or a hypomania episode within seven to 14 days after start of therapy. Prophylactic lithium is 70% to 80% effective in preventing or alleviating recurrences of mania, hypomania, and depression in unipolar and bipolar patients. Patients with full-blown mania may require antipsychotic therapy or antianxiety therapy in addition to lithium. Valproic acid and carbamazepine have also been found to be effective in treating mania.
Lithium dosing is individualized according to age, weight, salt intake, renal clearance, and clinical state. Short-term lithium side effects of nausea, diarrhea, anorexia, or abdominal pain occur in 10% to 30% of patients, but these effects are usually mild and transient. When nausea is bothersome, lithium can be taken after a meal or snack. A smaller, more frequent dose or an extended-release form will also help to alleviate nausea. About 30% of patients report muscle weakness and lethargy, but symptoms are most often transient. Polydipsia with polyuria and nocturia are common initially, but these side effects diminish with time. Up to 40% of patients complain of headache, memory impairment, mental confusion, decreased concentration, and impaired fine motor coordination.
During the first week of therapy, up to 50% of patients report a fine hand tremor at rest and with voluntary movement. This effect decreases with time. However, stress, concomitant drug therapy with antidepressants or antipsychotics, caffeine, sympathomimetics, or impending toxicity increase tremor. Tremor is reduced by lowering the dose, dividing the dose to decrease the level at peak concentration, switching to an extended-release product, or adding a beta-blocker. Lithium toxicity symptoms range from mild to severe. Mild toxicity symptoms include memory and concentration problems, fine hand tremor, GI upset, muscle weakness, and fatigue. Moderate to severe toxicity symptoms include agitation, confusion, lethargy, ataxia, dysarthria, aphasia, speech impediment, nystagmus, headache, vomiting, increased deeptendon reflexes, tremors, and involuntary movements. In the elderly, therapeutic levels can cause neurotoxicity characterized by confusion, memory impairment, agitation, electroencephalographic changes, and extrapyramidal symptoms.
Routine monitoring of lithium therapy often includes complete blood count (CBC), weight, serum electrolytes, thyroid panel, and tests of renal function (serum creatinine, 24-hour creatinine clearance, urinalysis). This is because lithium taken long term can cause reversible leukocytosis, weight gain, renal damage, thyroid damage, and cardiac effects. During maintenance therapy, lithium blood levels are measured every one to three months until stable for a year. If levels are stable, the monitoring interval can be extended to six to 12 months. Because lithium therapy is long term and there are many "twists and turns" in therapy, building rapport with the patient is important. Key components of patient education should include the following: the importance of taking medication regularly; the importance of lab tests to detect adverse effects, the symptoms of toxicity; the need for adequate fluid and sodium intake; the need to avoid excessive consumption of coffee, tea, cola, or other caffeinated beverages; and the fact that alcohol can increase toxicity. Women of childbearing age need to know that lithium can cause birth defects. As lithium has numerous drug interactions (Table 6 shows only selected significant interactions), it is important that patients always inform their physicians that they are taking lithium when new medicines are prescribed.
Although lithium is the treatment of choice for mania, carbamazepine and valproate are sometimes used instead of lithium or, in some patients, in addition to lithium.
Carbamazepine should be taken with meals to minimize GI side effects. In the early part of therapy, carbamazepine causes nausea, vomiting, abdominal pain, diarrhea, constipation, and anorexia in up to 15% of patients.
CNS toxicity can occur in up to 60% of patients treated with carbamazepine. Neurologic side effects including drowsiness, dizziness, fatigue, clumsiness, blurred or double vision, nystagmus, dysarthria, confusion, or headache can occur during the first few weeks of therapy. These side effects can be minimized by starting the patient on a low dose and gradually increasing to therapeutic levels. A dose reduction or a larger bedtime dose may also relieve side effects.
Between 8% and 15% of patients taking carbamazepine develop skin hypersensitivity reactions. Carbamazepine may cause syndrome of inappropriate antidiuretic hormone or water intoxication. Patients who complain of fatigue, irritability, or decreased concentration should be evaluated for hyponatremia/hyposmolarity. Liver function should be monitored yearly during carbamazepine therapy, to screen for a rare but potentially fatal granulomatous hepatitis.
Patients with low-normal or below-normal white blood cell count (WBC) and neutrophil counts at initiation of carbamazepine therapy have increased risk of developing leukopenia, so these patients should have frequent lab tests (every two weeks for the first one to three months). If a transient decrease in WBC and platelets occurs during the first few months of treatment, therapy discontinuation is not required.
Bone marrow suppression is a rare side effect of carbamazepine therapy. If symptoms of bone marrow suppression occur (sores, infections, fever, fatigue, petechiae, or easy bruising), a CBC with differential, platelet count, and liver enzymes is performed to rule out aplastic anemia, agranulocytosis, or thrombocytopenia. The highest risk for hematologic reactions is during the first year of treatment, so during the first year of therapy, patients are monitored closely. Carbamazepine is associated with teratogenicity.
Carbamazepine interacts with a number of drugs because it enhances the hepatic microsomal enzyme system. Carbamazepine toxicity can be caused by erythromycin, isoniazid, diltiazem, fluoxetine, lamotrigine, propoxyphene, TCAs, and verapamil. Carbamazepine can decrease effectiveness of oral anticoagulants, clozapine, cyclosporine, doxycycline, and valproic acid.
Valproic acid was originally marketed as an anticonvulsant. It is manufactured in several forms: sodium valproate, valproic acid, and divalproex sodium. Divalproex sodium, a delayed-release form, was approved by the Food & Drug Administration in 1995 as a mood stabilizer for the treatment of mania associated with bipolar disorder.
The most frequent adverse effects with valproic acid are GI upset and sedation. GI upset can be minimized by giving the drug with food, by using lower initial doses with gradual increases, or by using the delayed-release form. Other side effects of valproic acid include drowsiness, ataxia, lethargy, fine hand tremor, alopecia, and weight gain. As thrombocytopenia may occur at higher doses, patients should be monitored for bruising or bleeding. Liver function tests should be performed at baseline, then at six- to 12-month intervals to monitor changes in liver function. Valproic acid is associated with a 1% to 2% risk of neural tube defects.
Valproic acid has several significant drug interactions. They include the following: valproic acid increases the effects of barbiturates; valproic acid increases the effects of benzodiazepines; it increases the toxicity of carbamazepine and clonazepam; and it increases the free concentrations of hydantoins. Felbamate or salicylates administered with valproic acid increase the concentration of valproic acid. Antipsychotic therapy
Antipsychotic drugs can effectively reduce psychotic symptoms that occur due to several disorders, including schizophrenia, schizoaffective disorder, affective disorders, and organic mental disorders. Patients experience calming shortly after receiving antipsychotic drugs; however, actual improvement in psychosis is often delayed for days to weeks after the initiation of therapy.
Schizophrenia is typically considered in three phases, the acute phase, the resolving phase, and the stable phase. In the acute phase (which lasts from four to eight weeks), the patient has acute psychotic symptoms. The patient may have delusions, disorganized speech, hallucinations, behavior disturbances, and illusions. As the episode resolves (which lasts from two to six months), symptoms are improved but the patient is vulnerable to relapse if the drug dose is reduced or the patient encounters environmental stress. A patient in the stable phase (indefinite length of time) will have minimal symptoms from the acute stage; however, negative symptoms (lack of speech, social isolation, lack of pleasure, flat reactions, lack of will) may characterize his behavior.
Adherence to drug therapy is important in schizophrenia in order to prevent a relapse. Double-blind studies indicate that without maintenance therapy, only a relatively small number of patients who have experienced a first episode will fail to experience a second episode within the next three years.
Working with a schizophrenic patient is not easy, even for a psychiatrist. Pinals and Breier, writing in a textbook of psychiatry (Psychiatry, 1997 by Tasman, Kay, Lieberman), note that the foundation of treatment, the relationship between a patient and a psychiatrist, is difficult to achieve. Paranoid delusions can cause the patient to distrust the psychiatrist. Conceptual disorganization and cognitive impairment may make it difficult for the patient to follow even simple directions. Lack of emotional expression and social withdrawal can be demoralizing for the psychiatrist who is attempting to "connect" with the patient. Psychiatrists are advised to provide constancy, acceptance, nonintrusiveness, and-most important-caring.
The altered mental perception of a schizophrenic patient often means that the patient will be less informed and less able to be informed about his illness or treatment than a nonpsychotic patient. Even if given information, a schizophrenic patient may not apply it rationally. Thus, depending on the phase of the illness and the severity of symptoms, the patient's family, case manager, or even the court will be involved in the patient's drug therapy. Pharmacists will be most effective in promoting adherence to therapy by the patient when the caregiver(s) are knowledgeable about drug therapy. Antipsychotic drugs and relative side effects of sedation, extrapyramidal symptoms, anticholinergic effects, and cardiovascular effects are shown in Table 7. Treatment modalities for extrapyramidal symptoms are shown in Table 8.
Extrapyramidal symptoms typical of antipsychotic medicines include dystonias, pseudoparkinsonism, akinesia, and akathisia. Dystonias are involuntary muscle spasms that can be brief or sustained and involve any muscle group. They can develop suddenly (usually within 24-96 hours of administration of a dose or of a dose increase) and are quite frightening to the patient. Additionally, pharyngeal-laryngeal dystonias can be life-threatening. Risk factors for dystonia include younger patients (especially males) and the use of high-potency agents and high dosage. As higher-potency agents have become available, the risk for dystonia may approach 64%. Acute symptoms are treated with intramuscular or intravenous anticholinergic agents or benzodiazepines. Some physicians treat patients with anticholinergic medicine prophylactically to prevent symptoms.
Pseudoparkinsonism and akinesia are similar to the symptoms of Parkinson's disease (muscle rigidity, tremor, and bradykinesia). The incidence ranges from 15% to 36%, depending on the medication used. Increasing age and possibly female gender increase the risk of this side effect. Pseudoparkinsonism can be effectively treated with anticholinergic medication.
Akathisia is a motor restlessness that is often mistaken for agitation. It occurs in 25% to 36% of patients treated with high-potency agents. Akathisia does not respond well to treatment with anticholinergic agents. Reducing the dosage of the causative drug is the best intervention; however, this is not always possible. Patients are sometimes switched to a lower-potency drug. Chronic akathisia that fails to respond to multiple interventions may justify a trial of clozapine therapy. Akathisia is commonly treated with benzodiazepines or beta-blockers.
Tardive dyskinesia occurs late in antipsychotic therapy. It is characterized by abnormal involuntary movements, classically of the mouth and tongue or the mouth and face. The first detectable signs of tardive dyskinesia are mild forward, backward, and lateral movements of the tongue. As the disorder progresses, movement becomes more pronounced and may interfere with a patient's ability to chew, speak, or swallow. Facial and truncal movements may become evident. The mean incidence of tardive dyskinesia is 20%. Early signs of tardive dyskinesia may be reversible after drug cessation, but if not detected early, the movements become irreversible. Risk factors include increasing age, female gender, and organic mental disorder or mood disorder. Duration of antipsychotic therapy, daily dosage, and perhaps total cumulative dosage are the most significant risk factors, although persistent dyskinesias can occur in as little as six months of treatment.
Tardive dyskinesia can be prevented by using antipsychotic drugs only when they are the drugs of choice. A patient treated with an antipsychotic for more than three months should be reassessed for the need for continued treatment. Schizophrenic patients should occasionally have a trial of drug tapering and possibly drug discontinuation if the patient's clinical symptoms allow. Although there are no FDAapproved agents for treatment of tardive dyskinesia, potential treatments include clozapine, reserpine, alpha-methyldopa, amantadine, bromocriptine, levodopa, physostigmine, choline, lecithin, baclofen, valproic acid, benzodiazepines, lithium, beta-blockers, clonidine, papaverine, cyproheptadine, alpha-tocopherol, and calcium-channel blockers.
Sedation is a side effect that occurs more frequently with chlorpromazine, thioridazine, mesoridazine, and clozapine. Administering most or all of the dosage at bedtime can decrease daytime sedation. Sedation typically occurs early in treatment and may decrease over time. Anticholinergic side effects can be managed by treating the symptoms. Dry mouth can be minimized by increased intake of fluids, oral lubricants, ice chips, or the use of sugarless chewing gum or hard candy. Constipation can be treated by increases in fluid intake, dietary fiber intake, and exercise. Changes in visual accommodation, although bothersome, are usually temporary.
Patients and/or their families should be educated about the effects of antipsychotics on day-to-day living. Patients taking antipsychotic medication have poor body temperature adjustment. This means that in hot weather or during exercise, they fail to sweat properly and can overheat, even to the point of heatstroke. It also means that in cold weather hypothermia is a problem, especially in the elderly. Neuroleptic malignant syndrome, though uncommon, is serious. It manifests as high body temperature, rigidity, altered consciousness, sweating, fast heart rate or breathing, and urinary or fecal incontinence. Although improved treatment has decreased mortality from 20% in the 1980s to the present rate of 4%, early recognition and discontinuation of the antipsychotic drug is important.
Postural hypotension can be minimized by slow changes in posture and the use of support hose. For most patients, tolerance to this effect develops in two to three months.
Antipsychotic drugs are associated with teratogenicity, but experts differ over the risk. Ideally, antipsychotic drugs should be avoided in the first trimester. When that is impossible, first trimester exposure to the lowest dose for the shortest possible time is essential. Some authorities recommend discontinuation of medication five to 10 days before delivery to minimize the chances of neonatal extrapyramidal symptoms. With dose minimization and careful monitoring of the baby, patients taking neuroleptic agents can breast-feed an infant with relative safety. However, the American Association of Pediatrics classifies haloperidol as an agent of unknown effect, which may be of concern in a nursing infant.
Drug interactions with antipsychotic drugs are often additive with CNS effects or with anticholinergic effects. These drugs are often given with other psychoactive drugs, and their interactions have been described earlier. Of note, smoking is a potent inducer of hepatic enzymes and may increase clearance of antipsychotic drugs by as much as 50%.
Although lab tests monitoring for adverse effects of antipsychotic drug therapy are important, tests for monitoring clozapine are particularly stringent. Patients taking clozapine are required to have weekly blood tests to monitor for agranulocytosis. Clozapine tablets are available only through a special program designed to ensure compliance. Patients should be made aware of the risk of developing agranulocytosis while taking clozapine and should contact their physician immediately if they notice lethargy, weakness, fever, sore throat, malaise, ulcers in the mucous membranes, or other signs of infections. In addition, the possibility of seizures is significant during therapy. For this reason, patients should be warned about driving or performing hazardous activities during therapy. Special populations and psychoactive therapy Perhaps more than with any other class of drug therapy, psychoactive drugs are being evaluated to determine the effects of gender and ethnicity upon response. Research has already proven that men and women differ in response to therapy. For example: Young women show greater improvement and more severe adverse effects than men when treated with antipsychotic agents such as chlorpromazine.
Thiothixene clearance is higher in men than in women, and fluphenazine concentrations are higher in women than in men after identical dosage and adjustment for weight differences.
Men may respond better to imipramine than do women. Depressed men suffering from panic attacks seem to respond better to TCAs, while women with similar symptoms respond better to MAO inhibitors. Women may also exhibit a greater response to serotonin agonists and SSRIs than do men.
Diazepam has a higher clearance in younger women than in men. The statistical difference disappears in women who are 62-84 years old. Oral contraceptives decrease the clearance of benzodiazepines. Some researchers speculate that oral contraceptives decrease the rate of absorption of diazepam, leading to a slower onset of peak effect. One study showed that in women taking oral contraceptives, cognitive and psychomotor tasks were more impaired during the week of no hormone intake, because the benzodiazepines peaked more quickly.
At present, the clinical significance of these differences has not been determined. Gender differences will be most important in determining doses in drugs with a narrow therapeutic range. Sex differences in clearance may also be related to the higher incidence of adverse drug reactions observed in men than in women.
Emerging research also suggests that differences in psychotropic response is determined by ethnicity. For example, studies of the pharmacokinetics of normal Asian volunteers and schizophrenic patients found they had about 50% higher plasma concentration than their Caucasian counterparts when given comparable medication doses. Early reports from Japan regarding the need for lower doses of lithium and lower therapeutic lithium levels among Asians have been replicated in Taiwan, mainland China, and Hong Kong. Pharmacokinetic profiles of lithium were comparable in all groups; however, Asian patients appeared to have increased CNS response. Pharmacokinetic studies have also suggested Asians are more sensitive to benzodiazepines. Conclusion
Mental illness poses a complex series of treatment challenges. So great are the needs for professional assistance in psychopharmacy that the Board of Pharmaceutical Specialties has recently recognized psychiatric pharmacy as the newest specialty area. As a readily accessible health-care professional, the pharmacist is in a unique position to promote mental health, to educate and assist patients who have mental illness, and to use professional skills to enhance the pharmacist's role as a member of the health-care team. References are available on request.
COUNSELING A PATIENT WITH DEPRESSION Patients must be reminded that antidepressants treat a physical cause of depression. Depression is not a personality flaw or weakness.
All antidepressants take several weeks to reach full effect. Once the patient feels better, it is important to continue taking medicine for the full course of therapy to prevent return of symptoms. Antidepressant drugs are not addicting. They are not stimulants. Instead they act to return moods to normal. Patients should be given likely side effects rather than a compendium of side effects. Reassuring patients that side effects diminish with time or dosage adjustment is helpful in obtaining adherence to therapy.
Antidepressants can cause dizziness or drowsiness and may affect ability to drive a vehicle or operate machinery. Drinking alcohol may worsen depressed mood. Monoamine oxidase inhibitors (MAOIs) *Counsel patients to follow diet given by physician. *Patients must be cautioned about the possibility of drug interactions with nonprescription medicine. Patients should consult a doctor or R.Ph. before self-medicating.
*If patient develops a severe, pulsating headache, stiff neck, nausea, vomiting, or sweating, and blood pressure is sharply increased, a physician should be contacted immediately. Tricyclic antidepressants (TCAs)
Tricyclic antidepressants increase the risk of low blood pressure, which can cause fainting. Instruct patients about how to avoid problems-arise slowly from lying down and avoid prolonged bed rest. Tilting the head of the bed upward helps to prevent low blood pressure. Drinking adequate fluid helps to prevent low blood pressure.
*Common side effects of TCAs include dry mouth, constipation, drowsiness, dizziness, or increased appetite. Drinking alcohol with this drug will increase dizziness and drowsiness. *TCAs should not be discontinued abruptly. Selective serotonin reuptake inhibitors (SSRIs) *Most common side effects of SSRIs are mild. They include nausea, vomiting, diarrhea, and headache. *If nausea occurs, medicine should be taken with food. *Sertraline should always be taken with food for best absorption. Venlafaxine
*Venlafaxine can cause hypertension. Patients taking the drug should monitor blood pressure regularly and report sustained increases to their physicians.
*Venlafaxine can cause nausea. If nausea occurs, venlafaxine should be taken with food.
By Kathy Hitchens, R.Ph., WriteRx Medical Communications, Carmel, Ind.…
Questia, a part of Gale, Cengage Learning. www.questia.com
Publication information: Article title: The Pharmacist's Role in Mental Health. Contributors: Kathy Hitchens - Author. Magazine title: Drug Topics. Publication date: April 1997. Page number: S28+. © Advanstar Communications, Inc. Jan 2009. Provided by ProQuest LLC. All Rights Reserved.
This material is protected by copyright and, with the exception of fair use, may not be further copied, distributed or transmitted in any form or by any means.