Akathisia with antipsychotics

Akathisia has been reported in 16% of patients taking olanzapine (SEDA-21, 56). Three patients developed severe akathisia during treatment with olanzapine (20-25 mg/day) (87). In two, the akathisia resolved after withdrawal of olanzapine and in one of those olanzapine was well tolerated when reintroduced in combination with lorazepam. In the third patient, the akathisia was controlled by dosage reduction. A 33-year-old man with AIDS and a prior history of extrapyramidal symptoms with both typical antipsychotic drugs and risperidone developed dose-dependent akathisia with olanzapine 15-19 mg/day the akathisia responded to dosage reduction and beta-blockade (88). 

Antidepressants are commonly used in combination with antipsychotics to treat depressive symptoms in individuals with schizophrenia. Different antidepressants have been reported to inhibit metabolism of different P450 pathways. Table 66-10 summarizes the potential metabolic drug interactions between antidepressants and SGAs. Potential enzyme inhibitor interactions with clozapine are the most clinically significant. Increased clozapine serum concentrations with a CYP 1A2 inhibitor such as fluvoxamine may precipitate seizures. With the newer atypical antipsychotics, enzyme inhibitors are more likely to cause side effects such as increased sedation, orthostatic hypotension, or increased risk of akathisia and other extrapyramidal side effects. 

Among the most significant adverse reactions associated with the antipsychotic dm are the extrapyramidal effects. The term extrapyramidal effects refers to a group of adverse reactions occurring on the extrapyramidal portion of the nervous system as a result of antipsychotic drains. This part of the nervous system affects body posture and promotes smooth and uninterrupted movement of various muscle groups. Antipsychotics disturb the function of the extrapyramidal portion of the nervous system, causing abnormal muscle movement. Extrapyramidal effects include Parkinson-like symptoms (see Chap. 29), akathisia, and dystonia (see Display 32-1). 

Treatment with AChs is disappointing, and reduction in antipsychotic dose may be the best intervention. Another alternative is to switch to an SGA, although akathisia occasionally occurs with the SGAs. Quetiapine and clozapine appear to have the lowest risk for causing akathisia. 

Akathisia. This is a restless inability to sit still. It is an extremely nnpleasant sensation that can arise when a patient is treated with an antipsychotic drng (this is... 

Two extrapyramidal conditions, acute dystonia and akathisia, occur early during treatment, while parkinsonism tends to evolve gradually over days to weeks. All three reactions occur most commonly with the high-potency antipsychotics (Table 34.1) and are related to high Dz-receptor occupancy. Acute dystonia, which occurs in about 5% of patients on antipsychotic therapy, consists of uncontrollable movements and distortions of the face, head, and neck. It can be treated with centrally acting an-timuscarinic agents, such as benztropine, while antipsychotic therapy is temporarily discontinued. When this reaction subsides, the anticholinergic can be withdrawn. 

Most antipsychotic drugs cause unpleasant subjective effects in nonpsychotic individuals. The mild to severe EPS, including akathisia, sleepiness, restlessness, and autonomic effects are unlike any associated with more familiar sedatives or hypnotics. Nevertheless, low doses of some of these drugs, particularly quetiapine, are used to promote sleep onset and maintenance, although there is no approved indication for such usage. 

In a double-blind, multicenter, randomized, placebo-controlled study, 140 patients with treatment-refractory schizophrenia were treated with NAC (2 g/day) as an add-on to their antipsychotic maintenance medication over a 24-week interval followed by a 4-week washout. NAC administration moderately improved the clinical outcomes on the basis of the Clinical Global Impression (CGI) Severity and Improvement scales, and reduced positive and negative symptoms scores (based on the Positive and Negative Syndrome Scale (PANSS)). In addition, the severity of abnormal movements measured by the Barnes Akathisia Scale was diminished. The moderate effects of NAC treatment on a refractory cohort of patients indicate that NAC is an effective add-on strategy for chronic schizophrenia, (Berk et al., 2008). 

Finally, of 192 patients who had remained symptomatically stable for at least 1 month with another major second-generation antipsychotic drug, olanzapine (mean age 38 years 63% men), 70% completed a 6-month study with injectable risperidone treatment-related adverse events were reported by 121 patients (63%), mostly anxiety (12%), exacerbation of disease (10%), insomnia (9%), depression (6%), and akathisia (5%) (231). 

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