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Antipsychotic Medications for Different Indications
Antipsychotic agents are effective for treating nearly every medical and psychiatric condition where psychotic symptom or aggression is the predominant feature. The development of second-generation antipsychotics has been a major clinical advance for the treatment of schizophrenia. At present, these second-generation drugs are being used for schizophrenia as the first-line treatment, and are being used increasingly for various conditions beyond schizophrenia as happened with the first-generation anti-psychotics (Marder, 1997; Glick et al., 2001). The low incidence of EPS and TD associated with second-generation agents is highly beneficial in several neuropsychiatric conditions. A summary of various indications for second-generation antipsychotics is shown in Table 77.2. Some uses have gained general acceptance, whereas others depend on moderate or preliminary evidence.
Nearly all acute episodes of schizophrenia and schizoaffec-tive disorder, including first episode psychosis and recurrence in chronic schizophrenia, should be treated with antipsychotic medications (American Psychiatric Association, 2000). The psy-chiatrist should evaluate the patient’s mental status and physical condition before establishing a baseline for the administration of antipsychotic medications. Once the patient is diagnosed, pharmacotherapy should be applied as early in this phase as possible.
Continuous medications may be preferable for most pa-tients with schizophrenia, even if they are symptom free, to re-duce the likelihood of relapse.
Clear psychotic symptoms, such as delusions or hallucinations, are observed in approximately 25% of patients with major de-pressive disorder (Rothschild, 1996). These symptoms often respond poorly to antidepressants when they are administered alone, and may require the use of adjunctive antipsychotic agents (Marder, 1997). Conventional antipsychotic drugs are likely to expose patients to the development of TD and EPS, which may occur more frequently in patients with affective disorders than in those with schizophrenia (Casey, 1999). Thus, second-generation antipsychotics may have a more beneficial effect for this patient population.
There is clinical evidence that some of the second-genera-tion antipsychotics may have antidepressant effects in addition to their antipsychotic properties, and thus may improve depres-sive symptoms in schizophrenia (Tollefson et al., 1999; Buckley, 2001). Although depressive symptoms have traditionally been treated with antidepressants, a number of case reports and open trials have shown risperidone and olanzapine to be efficacious as monotherapy or adjunctive treatment for the treatment of de-pression without psychotic features (Jacobsen, 1995; Ostroff and Nelson, 1999) (for review, see Buckley, 2001).
In almost 50% of manic episodes, clear psychotic symptoms, such as delusions or hallucinations, are observed (Goodwin and Jamison, 1990). Antipsychotic medications can effectively treat the symptoms of acute mania, particularly in patients, who present with prominent agitation, in advance of the onset of action of lithium or mood stabilizers (Marder, 1997; Buckley, 2001). Over the past few years, second-generation antipsychotics have gained increasing favor over the conventional neuroleptics for the treatment of bipolar disorder because of their fewer EPS, a presumably lower risk of TD, and antimanic or mood stabilizing effects (Thase and Sachs, 2000). Currently, second-generation antipsychotics are being used as second-choice treatments for bipolar disorder and/or adjunctive therapy with lithium, carbamazepine, or sodium valproate (Ghaemi, 2000).
Tourettes’s disorder is a neurobehavioral disorder characterized clinically by motor and vocal tics (Jimenez-Jimenez and Garcia-Ruiz, 2001). Tics are usually present in childhood and may per-sist throughout life. The pathophysiology of the illness is not well known. When the tics interfere with the functioning of the patient, an antipsychotic medication can be effective in reduc-ing the severity of both motor and vocal tics (Marder, 1997). Al-though haloperidol and pimozide have been the most commonly used agents for the disease, second-generation antipsychotics are considered as promising agents for the control of tics, because of their better adverse event profiles.
A variety of substances, including amphetamines, cocaine, alco-hol and phencyclidine, can cause schizophrenia-like symptoms that occur while the patient is intoxicated or during drug with-drawal (Marder, 1997). While clinical trials have not yet estab-lished the efficacy of the second-generation antipsychotics for substance use disorders, several case reports and open-labeled studies offer suggestions of the effectiveness of new agents in these off-label uses (Misra and Kofoed, 1997; Smelson et al., 1997).
Dementia, whether due to Alzheimer’s disease or other causes, is frequently associated with behavioral disturbance, agitation and psychotic phenomena (e.g., persecutory delusions, hallucinations) (Stoppe et al., 1999). The management of behavioral disturbance and psychosis in the elderly is complicated by age-related decline in drug metabolism, vulnerability to drug–drug interactions, high incidence of concomitant physical illnesses and heightened sen-sitivity to EPS and TD (Marder, 1997; Buckley, 2001). Usually, lower dosages are more necessary for the elderly than for younger patients. Although evidence from a number of double-blind stud-ies supports the efficacy of traditional antipsychotics for treat-ing agitated elderly patients, the use of older agents is limited by EPS, TD, anticholinergic adverse effects, sedation, and orthos-tatic hypotension, which may result in falls and fractures.
Patients with Parkinson’s disease (PD) are sometimes accompa-nied with psychotic symptoms. Second-generation antipsychot-ics can offer a true benefit to this patient population (Friedman and Factor, 2000). Patients with Huntington’s disease (HD) can also benefit from antipsychotic medications (Marder, 1997). As with PD, the use of conventional agents worsens chorea move-ment disturbance (Buckley, 2001).
Children with schizophrenia may need neuroleptics for a long term. At present, no controlled trials have been published on the use of risperidone, olanzapine, quetiapine, or ziprasidone for the pediatric population with schizophrenia, thus definitive evidence is lacking. A number of open clinical trials and case reports of these new agents, however, indicate a possible effectiveness, though pediatric patients seem to have a greater propensity than adults for side effects, particularly EPS, weight gain and dyspho-ria, but also prolactin increase and white blood count aberrations (Kumra et al., 1998; Toren et al., 1998; Wudarsky et al., 1999; McConville et al., 2000).
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