Clozapine Anticholinergics

Urinary hesitancy and retention is reported with low-potency FGAs and with clozapine. Anticholinergic effects canse smooth mnscle slowing and paralyze the detrusor muscle of the bladder, requiring greater mine volume to evoke muscle contraction. Men with benign prostatic hypertrophy are especiaUy prone to this effect. ... 

The case in context Clozapine is a newer antipsychotic that can, like other agents in its class, produce antimuscarinic side effects. Although Ms. Doe had not complained of anticholinergic effects prior to beginning treatment with a moderate dose of diphenhydramine, it is likely that the additive anticholinergic effects of clozapine and diphenhydramine resulted in urinary retention. 

The four drugs were administered by psychiatrists blinded to treatment group assignment of patients. The 14-week study consisted of an 8-week dose escalation and fixed dose and a 6-week variable-dose period. The mean dose levels (mg/day) of the four compounds after the first 8 weeks were 452 for clozapine. 20.2 for olanzapine. 8.3 for risperidone and 19.6 for haloperidol. Patients on haloperidol received prophylactic anticholinergic medication to prevent extrapyramidal symptoms, and a few other drugs were permitted to treat agitation and insomnia. 

Clozapine also has been shown to benefit schizoaffective and bipolar patients with treatment-refractory mania ( 54) patients with Parkinson s disease and those with other neurological disorders with psychoses, such as Huntington s disease. Although clozapine has been shown to be an effective agent in the elderly, its usefulness in this population is limited because of its anticholinergic, sedative, cardiovascular, and potentially toxic effects on the bone marrow ( 55). In a study of 12 elderly female psychotic patients on clozapine (maximal daily dose, 300 mg), for example, five were taken off clozapine because of postural hypotension, one had a nonfatal episode of agranulocytosis, and one had leukopenia ( 56). 

DeLeon J, Stanilla JK, White AO, et al. Anticholinergics to treat clozapine withdrawal [Letter]. J Clin Psychiatry 1994 55 119-120. 

Gardner, Eliot L., Leslie S. Walker, and William Paredes. 1993. "Clozapine s Functional Mesolimbic Selectivity Is Not Duplicated by the Addition of Anticholinergic Action to Haloperidol A Brain Stimulation Study in the Rat." Psychopharmacology 110 119-24. 

Clozapine s anticholinergic effects can cause confusion and delirium as well as sedation and lethargy. The severity of withdrawal psychosis may be due to cholinergic rebound. Clozapine can aggravate or cause hypersalivation, glaucoma, constipation and ileus, and urinary retention (Baldessarini et al., 1991). Weight gain is also a potentially very serious problem. 

Toxic delirium caused by neuroleptic drugs with potent anticholinergic properties has been widely reported (SED-11,107), and has been reported with low-dose clozapine (406). 

Tracy JI, Monaco CA, Abraham G, Josiassen RC, Pollock BG. Relation of serum anticholinergicity to cognitive status in schizophrenia patients taking clozapine or risperidone. J Clin Psychiatry 1998 59(4) 184-8. 

Rebound psychosis or delirium or both have been reported after withdrawal of clozapine (207-212). Clozapine withdrawal has also been associated with nausea, vomiting, diarrhea, headache, restlessness, agitation, and sweating (213,214), which occur as the result of cholinergic rebound and which may respond to anticholinergic drugs (215), and with dystonias and dyskinesias. Delirium and the return of dyskinetic movements can occur within days after clozapine withdrawal. 

Anticholinergics to treat clozapine withdrawal. J Clin Psychiatry 1994 55(3) 119-20. 

Chengappa KN, Pollock BG, Parepally H, Levine J, Kirshner MA, Brar JS, Zoretich RA. Anticholinergic differences among patients receiving standard clinical doses of olanzapine or clozapine. J Clin Psychopharmacol 2000 20(3) 311-6. 

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