Constipation with antipsychotics

Other agents are also used for the treatment of manic-depressive disorders based on preliminary clinical results (177). The antiepileptic carbamazepine [298-46-4] has been reported in some clinical studies to be therapeutically beneficial in mild-to-moderate manic depression. Carbamazepine treatment is used especially in bipolar patients intolerant to lithium or nonresponders. A majority of Hthium-resistant, rapidly cycling manic-depressive patients were reported in one study to improve on carbamazepine (178). Carbamazepine blocks noradrenaline reuptake and inhibits noradrenaline exocytosis. The main adverse events are those found commonly with antiepileptics, ie, vigilance problems, nystagmus, ataxia, and anemia, in addition to nausea, diarrhea, or constipation. Carbamazepine can be used in combination with lithium. Several clinical studies report that the calcium channel blocker verapamil [52-53-9] registered for angina pectoris and supraventricular arrhythmias, may also be effective in the treatment of acute mania. Its use as a mood stabilizer may be unrelated to its calcium-blocking properties. Verapamil also decreases the activity of several neurotransmitters. Severe manic depression is often treated with antipsychotics or benzodiazepine anxiolytics. 

FIGURE 11-8. Side effects of the conventional antipsychotics (part 1). In this diagram, the icon of a conventional antipsychotic drug is shown with its Ml anticholinergic-antimuscarinic portion inserted into acetylcholine receptors, causing the side effects of constipation, blurred mouth, dry mouth, and drowsiness. 

Catatonic schizophrenia is a controversial syndrome, and there is debate about its etiology and treatment. There has been a report of two cases of catatonic schizophrenia successfully treated with clozapine a 49-year-old woman and a 19-year-old man (18). Both responded to clozapine despite being resistant to several conventional and atypical antipsychotic drugs and, in the second case, a course of electroconvulsive therapy. These two cases are intriguing, because the dose of clozapine required to improve catatonia was about double the dose required to improve psychosis significantly (600 mg/day and 750 mg/day). The two patients had common adverse effects of clozapine the first had mild nocturnal hypersalivation and mild/moderate constipation, and the second had moderate nocturnal hypersalivation. 

Patients with AD are more sensitive to antipsychotic side effects than other patient groups. Increased sensitivity to antipsychotic side effects in the elderly appears to be the result of altered pharmacodynamics rather than altered pharmacokinetics. Particularly problematic side effects are extrapyramidal side effects, postural hypotension caused by a-adrenergic blockade, and anticholinergic effects, including increased confusion, urinary retention, constipation, and dry mouth. For a more detailed description of antipsychotic side effects see Chap. 66 on schizophrenia. Overall, fewer side effects are seen with tlie newer atypical antipsychotics, making them a preferred choice for treatment of psychosis or aggression in the AD patient. Effective doses of antipsychotic medications are much lower than those typically used to treat schizophrenia (see Table 63-8). The rule of thumb is to start low and go slow. ... 

Anticholinergic effects Adverse effects that result from the suppressive action of certain mental health medications (antipsychotic and antidepressant medications) as well as other general medications (antihistamines). This affects the action of acetylcholine in the brain and peripheral nervous system. The actual side effects include dry mouth, blurred vision, constipation, and urinary hesitancy. This could present a particular problem when working with older people. 

The use of antipsyehoties with antimusearinies can result in a generalised, low grade, but not usually serious, additive inerease in the antimuscarinic effects of these drugs (blurred vision, dry mouth, constipation, difficulty in urination, see Antimusearinies + Antimusearinies , p.674). However, sometimes serious intensifieation takes plaee. For the sake of clarity these have been subdivided here into (a) heat stroke, (b) constipation and adynamic ileus, (e) atropine-like psyehoses, (d) antagonism of antipsychotic effects and (e) miscellaneous effeets. 

Fluoxetine. The combination of perphenazine and fluoxetine was found to be effective in the treatment of psychotic depression in 30 patients, and the adverse effects (which included dry mouth, blurred vision, constipation, tremor or rigidity, orthostasis and hypotension) were thought to be easier to tolerate than an antipsychotic with a tricyclic antidepressant. However, one woman developed marked extrapyramidal symptoms within 2 weeks of starting perphenazine 4 mg twice daily and fluoxetine 20 mg daily. ... 

Placebo-coutroHed studies Quetiapine has been compared with placebo in the avoidance of relapses in patients in remission in a randomized, double-blind clinical trial [119 ]. Patients who had taken antipsychotic drugs for at least 1 year for first episode of psychosis took either maintenance quetiapine 400mg/day ( =89) or placebo (n = 89) and were followed for 12 months or until a relapse occurred. The Kaplan-Meier estimate of the risk of relapse at 12 months was 41% with quetiapine (95% CI=29%, 53%) and 79% (95% CI=68%, 90%) with placebo. The rate of withdrawal because of adverse or serious adverse events was greater with quetiapine (18% versus 8%) patients taking quetiapine reported more adverse reactions sleepiness or sedation, reduced salvation, and constipation). 

Antipsychotic drugs are more often used in the treatment of bipolar illness. Lithium was equivalent to aripiprazole, and both were superior to placebo, in a 3-week, double-blind, randomized, placebo-controlled study of acutely manic patients [5 ]. The improvement was maintained for an additional 9 weeks (a total of 12 weeks), with a 12.7 point drop in Young Mania Rating Scale score for lithium and a 14.5 point drop for aripiprazole. The most common adverse events with aripiprazole were headache, nausea, akathisia, sedation, and constipation and with lithium nausea, headache, constipation, and tremor. 

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