Testosterone for schizophrenia

About 1% of people suffer from schizophrenia, a serious mental illness found in all societies and cultures. Many treatments options are available to reduce the dramatic symptoms of this illness such as the false beliefs (delusions) and false or distorted perceptions (hallucinations). Other symptoms, such as emotional withdrawal and apathy are also often seen with schizophrenia and seem less responsive to treatment with antipsychotic drugs. In addition, some people continue to experience delusions and hallucinations despite adequate use of antipsychotic drugs and often supplementary treatments are used. These supplementary treatments include sex hormones such as estrogen and testosterone.

We reviewed the effects of dehydroepiandrosterone (DHEA)/testosterone as an adjunctive therapy to standard antipsychotic drugs for people with schizophrenia and found three relevant small, short studies. All trials compared antipsychotic drugs plus DHEA with antipsychotic drugs and placebo. Results are inconclusive, with most outcomes being either non-significant or contradictory and a much larger, conclusive study should be undertaken. Currently however, people with schizophrenia should only agree to take this experimental treatment within the context of a well designed experimental study. We found nothing in these studies to suggest that it should be used in routine care.

Authors' conclusions: 

Results are inconclusive with most outcomes being either non-significant or producing contradictory findings. Currently, adjunctive DHEA should remain an experimental treatment for people with schizophrenia.

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Background: 

Recently, sex hormones such as estrogens and testosterone or its derivatives have been the focus of interest for treatment of persistent symptoms associated with schizophrenia.

Objectives: 

To review the effects of dehydroepiandrosterone (DHEA)/testosterone as adjunctive therapy to standard antipsychotic drugs.

Search strategy: 

We searched the Cochrane Schizophrenia Group Trials Register (January 2007).

Selection criteria: 

We included all clinical randomised trials comparing DHEA/testosterone plus standard antipsychotic treatment with standard treatment alone.

Data collection and analysis: 

We independently selected studies and extracted data. For dichotomous data we calculated the relative risk (RR) and its 95% confidence interval (CI) on an intention to treat basis, using a fixed effects model. We presented continuous data using the weighted mean difference statistic, with a 95% confidence interval using a fixed effects model.

Main results: 

We found three relevant small, short trials (total n=126). Clinical Global Impression data were equivocal (n=27, 1 RCT, WMD -0.43 CI -0.9 to 0.1). Average total PANSS scores were not significantly different between the DHEA plus antipsychotic group and those given antipsychotic drugs and placebo (n=82, 2 RCTs, WMD -4.16 CI -13.8 to 5.5). PANSS positive scores were equivocal (n=55, 1 RCT, WMD -1.00 CI -3.8 to 1.8). For negative symptoms binary SANS scale data favoured the DHEA plus antipsychotic group (n=30, 1 RCT, RR 0.23 CI 0.1 to 0.6, NNT 2 CI 2 to 3) but PANSS negative scores were not significantly different between comparison groups (n=55, 1 RCT, WMD -2.30 CI -6.4 to 1.8). About 17% of people left both groups early (n=64, 2 RCTs, RR 0.80 CI 0.3 to 2.4). St Hans Rating Scale data for extrapyramidal symptoms favoured the DHEA plus antipsychotic group (n=30, 1 RCT, WMD -5.00 CI -8.8 to -1.2) but akathisia ratings were equivocal (n=34, 1 RCT, RR 2.67 CI 0.3 to 23.1). Ratings of parkinsonian movement disorder differed within the same trial depending of the outcome scale used. Quality of life seemed unaffected by use of DHEA (n=55, 1 RCT, WMD 6.20 CI -1.4 to 13.8).

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