Trifluoperazine versus placebo for schizophrenia

Trifluoperazine (trade name Stelazine) is a long-established antipsychotic drug that has been used since the 1950s to treat schizophrenia. It is one of the first generation (typical) drugs that have proven very effective for treating the ‘positive symptoms’ of schizophrenia, such as hearing voices, seeing things and having strange beliefs. These drugs may cause side effects such as involuntary shaking, restlessness and movement disorders such as having a strange posture.

There are also more modern drugs (second generation and atypical antipsychotic drugs). These are effective with the ‘positive symptoms’ of mental illness but also help treat ‘negative symptoms’ such as apathy, weight gain and loss of emotion in people with schizophrenia. These more modern drugs are much more expensive.

This review is based on a search for trials carried out in July 2012, and includes 10 studies with 686 participants. The aim was to determine the effects of trifluoperazine for schizophrenia when compared with placebo (a ‘dummy’ treatment). As expected, people given trifluoperazine showed a significant improvement compared to placebo in both the short and medium term, reinforcing the use of this well-established typical antipsychotic for people with schizophrenia. However, trifluoperazine can cause side effects such as confusion, agitation, having a dry mouth and blurred vision, but causes less sedation and dizzy spells, so is generally well tolerated by people with schizophrenia.

The authors of the review conclude that trifluoperazine has similar effectiveness to other common antipsychotic drugs, although it may cause more side effects. Evidence used in the review was also graded as low or very low quality. In the light of this, use of other antipsychotic drugs should be considered before starting on trifluoperazine. Most of the included studies were conducted roughly 40 years ago so new, large, comprehensive and independent research trials are needed.

This plain language summary has been written by a consumer Ben Gray from RETHINK.

Authors' conclusions: 

Our results agree with existing evidence that compared to placebo, trifluoperazine is an effective antipsychotic for people with schizophrenia. Furthermore, our review provides supportive evidence that trifluoperazine increases the risk of extrapyramidal adverse effects. Although the effect sizes against placebo are similar to those observed with other agents, they are based on data from many small, pre-CONSORT trials with generally either a low or very low GRADE evidence that has limited implication for clinical practice. Large, independent trials are needed that adhere to the CONSORT statement to compare trifluoperazine with placebo used in the treatment of schizophrenia and schizophrenia-like illnesses.

Read the full abstract...

Trifluoperazine is a long-established high potency typical antipsychotic drug used in the treatment of schizophrenia and schizophrenia-like illnesses.


To determine absolute effects of trifluoperazine for schizophrenia and schizophrenia-like illnesses compared with placebo.

To critically appraise and summarise current evidence on the resource use, cost and economic evaluation of trifluoperazine compared with placebo for schizophrenia.

Search strategy: 

Searches of the Cochrane Schizophrenia Group's register of trials (July 2012), supplemented with handsearching, reference searching, personal communication and contact with industry. Two review authors undertook a search for economic studies using the Cochrane Schizophrenia Group's Health Economic Database (CSzGHED) on the 9th April 2013.

Selection criteria: 

All available clinical randomised trials involving people with schizophrenia and schizophrenia-like illnesses that compare trifluoperazine with placebo.

Data collection and analysis: 

Studies for the effects of interventions were reliably selected by a review team and data were doubly independently extracted to reduce bias. We only used dichotomous data, using intention-to-treat analysis when possible. Data were estimated using risk ratio (RR) with 95% confidence intervals (CI). A 'Summary of findings' table was produced, where possible, for each primary outcome using GRADE. Economic studies were searched and reliably selected by review authors (VF and SS) to provide an economic summary of available data. Where no relevant economic studies were eligible for inclusion, the economic review team valued the already-included effectiveness outcome data to provide a rudimentary economic summary.

Main results: 

This review included 10 studies with a total number of 686 participants featuring in 20 different outcomes of interest. Overall, there was significant clinical improvement in clinical global state at medium term amongst people receiving trifluoperazine (3 RCTs, n = 417, RR 4.61, CI 1.54 to 13.84, low quality evidence) and significantly fewer people receiving trifluoperazine left the studies early due to relapse or worsening at medium term (2 RCTs, n = 381, RR 0.34, CI 0.23 to 0.49, low quality evidence). However, results were equivocal for leaving the study early at medium term for any reason (2 RCTs, n = 391, RR 0.80, CI 0.17 to 3.81, very low quality evidence) and due to severe adverse effects (2 RCTs, n = 391, RR 1.54, CI 0.56 to 4.24, very low quality evidence). Equivocal data were also found for intensified symptoms at medium term (2 RCTs, n = 80, RR 1.05, CI 0.54 to 2.05, very low quality evidence) and rates of agitation or distress again at medium term (1 RCT, n = 52, RR 2.00, CI 0.19 to 20.72, very low quality evidence). Comparison between low and high-dose trifluoperazine with placebo from a single study provided equivocal evidence of effects. For economic outcomes, we valued outcomes in GBP terms and presented them in additional tables; there was an estimated saving of £3488.3 in favour of trifluoperazine. However, numerous assumptions were made and these savings need to be interpreted in light of those assumptions.