Introduction: Given the limited range of effective drug treatments for patients with schizophrenia, increasing numbers of patients, often termed 'treatment-resistant' are prescribed clozapine. While the induction of neutropenia or agranulocytosis by clozapine is well appreciated, other rare potentially fatal adverse reactions may also occur including acute interstitial nephritis as reported in this case.

IntroductionGiven the limited range of effective drug treatments for patients with schizophrenia, increasing numbers of patients, often termed 'treatment-resistant' are prescribed clozapine. While the induction of neutropenia or agranulocytosis by clozapine is well appreciated, other rare potentially fatal adverse reactions may also occur including acute interstitial nephritis as reported in this case.Case presentationA 57-year-old Caucasian woman with treatment-resistant chronic schizophrenia developed acute renal failure following initiation of treatment with clozapine. The adverse reaction occurred after only four doses of the drug had been administered (titrated from 12.5 to 25 mg per day). After clozapine had been withdrawn, the patient's renal function returned to normal with no other changes to medication. The patient had been exposed to clozapine about 4 years previously when she had developed a similar reaction.ConclusionRenal reactions to clozapine are extremely rare but, if not recognized promptly, may prove fatal. Psychiatrists need to be aware of this possible complication when clozapine is initiated.

Introductionll antipsychotics act via dopaminergic receptor antagonism. This pharmacology is shared by all first (FGA) & second (SGA) generation antipsychotics. We reviewed the efficacy & safety of all antipsychotics in clinical use for BMJ Clinical Evidence (Barry et al 2012).Methods & questionsOur paper summarises key results from this systematic review based on comprehensive literature search of the Medline, Embase, Cochrane Library, and other databases including safety information from the FDA and MHRA in UK. The main clinical questions of interest were: What is the efficacy of drug treatments for positive, negative, or cognitive symptoms of schizophrenia? How effective are treatments for people with schizophrenia resistant to standard antipsychotic drugs?ResultsWe found 51 systematic reviews, RCTs, or observational studies that met our inclusion/quality criteria and performed GRADE analysis to assess quality of evidence. Key results are presented for efficacy & safety for: amisulpiride, chlorpromazine, clozapine, depot haloperidol, haloperidol, olanzapine, pimozide, quetiapine, risperidone, sulpiride, ziprasidone, zotepine, aripiprazole, sertindole, paliperidone, flupentixol, depot flupentixol, zuclopenthixol, depot zuclopenthixol, and clozapine.DiscussionThe evidence for some ‘standard’ treatments is surprisingly weak. Up to 1/3 -1/2 of patients fail to respond to currently available antipsychotics, and all antipsychotics cause side effects in most people. This downbeat conclusion is not surprising, given clinical experience and the common mechanism of action of all antipsychotics. More efficacious antipsychotic medication will only be developed from understanding the biological pathogenesis of schizophrenia.Barry S, Gaughin T, and Hunter R. Schizophrenia. BMJ Clinical Evidence 13 July 2012..