Chlorpromazine versus reserpine for schizophrenia

Review question
Is there historical evidence that the very first antipsychotic drug (reserpine) - which is now very rarely used - is effective compared with an antipsychotic drug that has stayed in use for over 60 years (chlorpromazine).

Background
Reserpine was discovered in the 1940s. It is a drug that stops some chemical functions in the brain for good so that even when the drug is stopped and out of a persons' system, the effect of the drug (good or bad) continues until the body replenishes its stores of the changed brain chemicals. This is not the case for chlorpromazine - a drug that came along a little later - the effect of which lasts only as long as the chemical is around in the body. Chlorpromazine's blockade of brain chemistry is reversible, reserpine's blockade is not.

Study characteristics
The review currently includes nine studies with around 60 participants per study. All of these studies are now over 60 years old, conducted between 1955 and 1962 and include people with the most severe illnesses.

Key results
Chlorpromazine does better than reserpine for 'improvement in global state' with most trials reporting on this outcome. There was no clear difference between the drugs for 'occupational adjustment', 'general behaviour', and, rather surprisingly, adverse events and finally, leaving the study early.

Quality of the evidence

Judged by standards of today, the evidence is largely of limited quality. However, some of these 1950s studies are remarkable in their foresight and clarity.

Authors' conclusions: 

Judged by standards of today, the evidence is largely of limited quality. However, some of these 1950s studies are remarkable in their foresight and clarity. Reserpine did have some effect on global state - but chlorpromazine did seem to perform better. Important issues regarding adverse effects were not really addressed by these trials. Chlorpromazine remains on the WHO list of essential drugs. Reserpine is now almost obsolete, although, probably as a result of evidence other than that reported in the pioneering trials used in this review.

Read the full abstract...
Background: 

In the 1940s reserpine, refined from a plant extract that had been used for centuries, began to be used as a treatment for people with mental disorders and was one of the very first antipsychotic drugs. Its irreversible pharmacological potency and adverse effects meant that it has been withdrawn in the UK and its role has been superceded by 'newer' compounds. The effects of reserpine are of historical interest although there are some reports of it still being used in highly specialist situations in psychiatry. Chlorpromazine is also an old drug but it is still used for treatment of people with schizophrenia.

Objectives: 

To investigate the effects of two old medications (reserpine and chlorpromazine) for people with schizophrenia. Reserpine is now rarely used while chlorpromazine remains on the essential list of drugs of the World Health Organization (WHO).

Search strategy: 

We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials (24 March 2016).

Selection criteria: 

We included randomised clinical trials focusing on chlorpromazine versus reserpine for schizophrenia that presented useable data.

Data collection and analysis: 

We extracted data independently. For binary outcomes, we calculated risk ratio (RR) and its 95% confidence interval (CI), on an intention-to-treat basis. We employed a fixed-effect model for analyses. We assessed risk of bias for included studies and created a 'Summary of findings' table using GRADE.

Main results: 

The review currently includes nine studies with an average 60 participants per study. All of these studies are now over 60 years old, conducted between 1955 and 1962. When chlorpromazine was compared with reserpine for people with schizophrenia, improvement in global state was better at short term for those receiving chlorpromazine (n = 781, 6 RCTs, RR 'not improved' 0.75 95% CI 0.62 to 0.92, low-quality evidence). Short-term improvement in paranoid distortion was measured using the Multidimensional Scale for Rating Psychiatric Patients (MSRPP). Data showed no clear difference between treatment groups (n = 19, 1 RCT, RR 1.33 95% CI 0.62 to 2.89, very low-quality evidence). There was no difference in functioning: occupational adjustment, medium term (n = 40, 1 RCT, RR 0.83 95% CI 0.47 to 1.47, moderate-quality evidence) and general behaviour (n = 98, 1 RCT, RR 0.79 CI 0.41 to 1.53, moderate-quality evidence). Adverse events were poorly reported. For 'toxic reaction' there was, again, no obvious difference between the two compounds (n = 210, 3 RCTs, RR 1.68 95% CI 0.43 to 6.54, moderate-quality evidence), and this also applied to leaving the study early (n = 229, 4 RCTs, RR 1.16 95% CI 0.94 to 1.42, moderate-quality evidence).

Share/Save