Perphenazine for Schizophrenia

A Cochrane review [Abstract] 1 included 4 RCTs with 365 participants. The size of the included studies was between 42 and 158 participants with a study length between 1 to 4 months. All studies were conducted in hospitals and carried out between 1961 and 1993. The attrition rate was from 15% to 89% in the studies for perphenazine (PPH).The effects of PPH and low-potency antipsychotic drugs (LPAD) seemed to be similar regarding response to treatment (PPH 58% vs. LPAD 59%, RR 0.97, CI 0.74 to 1.26; 2 RCTs, n = 138). There was no difference in acceptability in terms of participants leaving the studies early due to any reason (PPH 30% vs. LPAD 28%, RR 0.78, CI 0.35 to 1.76; 3 RCTs, n = 323).The figures for patients experiencing at least one adverse effect were PPH 33% vs. LPAD 47% (RR 0.83, CI 0.36 to 1.95; 2 RCTs, n = 165) and experiencing at least one movement disorder: PPH 22% vs. LPAD 0% (RR 15.62, CI 0.94 to 260.49; 1 RCT, n = 69). Akathisia was more frequent for PPH (PPH 25% vs. LPAD 22%, RR 9.45, CI 1.69 to 52.88; 2 RCTs, n = 227), whereas severe toxicity was less so (PPH 42% vs. LPAD 69%, RR 0.61, CI 0.41 to 0.89; 1 RCT, n = 96).There were 3 deaths for LPAD by 4 months but the difference between groups was not significant (PPH 0% vs. LPAD 2%, RR 0.14, CI 0.01 to 2.69; 1 RCT, n = 96). Data were not available for relapse, service use, costs and satisfaction with care.

Comment: The quality of evidence is downgraded by study quality (unclear allocation concealment, high drop-out rate) and indirectness (short follow-up time, only hospital patients).

A Cochrane review [Abstract] 2 included 31studies with a total of 4522 subjects. The ages ranged from 13 to 70 years.The duration of included trials covered a range from 10 days to 18 months, with the most common being 12 weeks. The longest study was 18 months.

• Perphenazine vs. placebo: significantly more people on placebo rated as either 'no better or deterioration' for global state than people on perphenazine (RR 0.32 CI 0.13 to 0.78; 1 RCT, n = 61). More people receiving placebo relapsed, although not a statistically significant number (RR 0.14 CI 0.02 to 1.07; 1 RCT, n = 48). Death was not reported in the perphenazine versus placebo comparison. Experiences of dystonia were equivocal between groups (RR 1.00 CI 0.07 to 15.08; 1 RCT, n = 48).
• Perphenazine vs. any other antipsychotic drugs: no real differences in effect between the drugs were found. There was no significant difference between groups for those considered 'no better or deterioration' (RR 1.04 CI 0.91 to 1.17; 17 RCTs, n = 1879). For mental state outcome of 'no effect' of the study drug, there was again no significant difference between groups (RR 1.24 CI 0.61 to 2.52; 4 RCTs, n = 383). Death was not reported in any of the included studies. There was no significant difference in rates of dystonia (RR 1.36 CI 0.23 to 8.16; 4 RCTs, n = 416), nor was there a significant difference between groups for serious adverse events (RR 0.98 CI 0.68 to 1.41; 2 RCTs, n = 1760).

Comment: The quality of evidence is downgraded by study quality (unclear allocation concealment) and indirectness (short follow-up time).

A Cochrane review [Abstract] 3 on depot perphenazine included 4 studies with a total of 313 subjects. The studies were carried out between 1979 and 1985. Three of the 4 studies (n=249) compared perphenazine enanthate to another depot antipsychotic. There was no clear difference between depots for outcomes such as death, global state, relapse or leaving the study early. Weak data does suggest that the enanthate ester may have more short-term adverse effects than its decanoate equivalent and than clopenthixol decanoate.

References

• Tardy M, Huhn M, Engel RR et al. Perphenazine versus low-potency first-generation antipsychotic drugs for schizophrenia. Cochrane Database Syst Rev 2014;10():CD009369. [PubMed]
• Hartung B, Sampson S, Leucht S. Perphenazine for schizophrenia. Cochrane Database Syst Rev 2015;3():CD003443. [PubMed]
• David A, Quraishi S, Rathbone J. Depot perphenazine decanoate and enanthate for schizophrenia. Cochrane Database Syst Rev 2005 Jul 20;(3):CD001717. [PubMed]