How to treat common side effects of clozapine? Int Cli Psychopharmacol. Nov. 2014

Clozapine has established superiority over other medications in treating resistant schizophrenia.  Clozapine has  many side effects. With appropriate monitoring clozapine is a safe and effective medication. It is important that clinicians have sufficient options to manage side effects that emerge during clozapine treatment.

Roi Sagya, Abraham Weizmana,and Nachum Katza report on the useful treatment options for side effects like hyper salivation, constipation, tachycardia and nocturnal enuresis.

Hypersalivation: This is often a reason for stopping the medication. It occurs in 30-80% of patients. There are medical & social implications .It is thought that swallowing is affected by clozapine ( rather than production). Treatment options: chewing gum ( promote swallowing),head  elevated position  during sleep ( if feeling suffocated), sleeping on side to avoid aspiration are useful strategies. Try to use the minimum effective clozapine dose. Anticholinergics ( biperidine, trihexyphenidyl) , central alpha 2 agonist clonidine or guanfacine can be tried. Remember that these agents can increase constipation and urinary retention.  Atropine ophthalmic drops can be used as mouth wash, this can also be combined with hyoscine. Botulinum injection in to parotid gland has been tried. Sulpiride and amisulpride are thought to reduce salivation. Moclobemide is also suggested as an option. There are no widely agreed guidelines on these various options.

Constipation: Anticholinergic and antiserotonergic effects result in constipation.This can lead to serious complications. Rate of death from constipation is three times than from agranulocytosis. High-fiber diets, proper hydration, and use of stool softeners and laxatives are the usual treatment options. Orlistat, lipase inhibitor, is found to be beneficial in one study.

Tachycardia: This can be related to dose and rate of dose increase. If severe or symptomatic treatment might be needed. Keeping dose low is the first step. Both Atenelol and  Propranalol are effective, atenelol penetrate Blood brain barrier less and is less likely to add to sedation.

Nocturnal Enuresis: Try lowest dose to see whether this disappears. Give less dose at night-time. Restrict fluids, avoid alcohol, coffee etc. Successful treatment with ephedrine, desmopressin,  anticholinergics, tricyclics,  and aripiprazole  are reported. desmopressin can cause hyponatremia.

Summary of the article: 

Pharmacological and behavioral management of some often-overlooked clozapine-induced side effects.

Sagy R, Weizman A, Katz N.

Int Clin Psychopharmacol. 2014 Nov;29(6):313-7.



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