Use of combined antipsychotics for patients with treatment-resistant/refractory schizophrenia is common practice in psychiatry. The objective of this paper is to review the current literature on combining non-clozapine atypical antipsychotics as well as discussing the theoretical benefits and risks, and summarizing the implications for clinical practice. We found in cases of treatment-resistant schizophrenia, where clozapine is deemed inappropriate, combination therapy with non-clozapine atypical antipsychotics is a strategy worthy of consideration. Combinations using olanzapine with either amisulpride or risperidone--or quetiapine with risperidone--in theory act on different receptor profiles and in the limited data available have shown improvement in symptoms, been used most frequently, and on balance have more data on safety. Initial case reports suggest that aripiprazole combined with non-clozapine atypicals may worsen psychosis. The current literature, however, has significant limitations. For this reason, due to the lack of data on safety, caution is recommended. There needs to be further well-designed studies with the aim to specifically investigate the effects of combination therapy to allow the clinician to better balance the risks and benefits (both clinical and economical) of treatment.

A drug-induced psychosis resembling paranoid schizophrenia can occur with repeated or high-dose use of methamphetamine. While this generally resolves rapidly with cessation of stimulant use, some cases of protracted drug-induced psychosis in vulnerable individuals have been documented. Behavioural sensitization can also occur, and neuroleptics may prevent the recurrence of further psychosis triggered by ongoing low-dose methamphetamine use.

Background. There is a body of literature on metamphetamine psychosis dating back to the 1950's with a recent resurgence of interest following increase in use worldwide. Distinct similarities appear to exist between metamphetamine psychosis and schizophrenia.Aims. The aim of this paper is to critically review the literature on metamphetamine psychosis.Method. Searches on Medline, Psycinfo and Cochrane were undertaken, references were followed and recent editions of major journals reviewed. There is a vast array of literature on stimulants and psychosis. I have deliberately limited my data to that on metamphetamines, only citing other data if particularly well known and relevant to distinguish. Data in Japanese has been quoted with reference to where cited.Results. Metamphetamine psychosis has been observed as a paranoid hallucinatory state developing gradually with repeated metamphetamine abuse and possibly continueing after metamphetamine withdrawal. Also noted is a lasting susceptibility to recurrence of the paranoid hallucinatory state with neuroleptics preventing this recurrence. Patients with persistent metamphetamine psychosis can develop long lasting residual symptoms resembling negative symptoms of schizophrenia.In animals intermittent administration of smaller doses of metamphetamine appears to lead to augmentation of behaviour, and increases in dopamine and seretonin levels. Also it appears that a challenge injection or stress can cause the same responses, which are inhibited by dopamine antagonists. Larger repeated doses of metamphetamine appear to lead to long lasting depletion of dopamine and seretonin.Conclusions and clinical importance. There are clear clinical similarities between metamphetamine psychosis and schizophrenia altered in both conditions with the use of antipsychotics. A major as yet unanswered question is whether metamphetamine can cause schizophrenia.The literature describes a number of changes in dopamine and seretonin systems. More research in this field could increase our understanding of transmitters and receptors, thereby helping our quest in improved drug development for both illnesses.Declaration of interest. Nil.

A drug-induced psychosis resembling paranoid schizophrenia can occur with repeated or high-dose use of methamphetamine. While this generally resolves rapidly with cessation of stimulant use, some cases of protracted drug-induced psychosis in vulnerable individuals have been documented. Behavioural sensitization can also occur, and neuroleptics may prevent the recurrence of further psychosis triggered by ongoing low-dose methamphetamine use.