Hypoalgesia in schizophrenia is independent of antipsychotic drugs: A systematic quantitative review of experimental studies

Diminished sensitivity to pain in schizophrenia has been reported since the early works of Bleuler [Bleuler E. Textbook of psychiatry (trans. Brill HA, 1951). New York: Dover Publications; 1911] and Kraepelin [Kraepelin E. Dementia praecox and paraphrenia. Edinburgh, Scotland: E and S Livingstone; 1919]. Over the last decade, experimental studies have measured pain perception in schizophrenia and produced mixed results. This meta-analysis sought to determine if the scientific literature confirms the hypothesized hypoalgesia in schizophrenia. The search was performed with computerised literature databases. A study was retained in the meta-analysis if: (i) it comprised a group of schizophrenia patients, compared to a control group of healthy volunteers; and (ii) pain was measured via experimental procedures (e.g. thermal, electrical, or mechanical stimuli). Using Comprehensive Meta-Analysis-2, effect size estimates of the differences in pain scores (all pain scores derived from all pain tests) between schizophrenia patients and healthy volunteers were calculated. Eleven studies were included in the meta-analysis. For the composite analysis, a positive, moderate, and significant effect size estimate emerged (N = 497; Hedges's g = 0.437; p = 0.005), suggesting that patients with schizophrenia show a diminished response to experimentally-induced pain. Secondary analyses showed that: (i) drug-free patients also have hypoalgesic responses; and that (ii) sensory thresholds are increased in schizophrenia patients. This meta-analysis substantiates the hypothesis of a diminished pain response in schizophrenia. The study also suggests that hypoalgesia in schizophrenia cannot be solely explained by the effects of antipsychotic drugs, and that it may not be a pain-specific blunted response. Further studies are warranted to determine the clinical and biological correlates, and the social and health consequences, of hypoalgesia in schizophrenia.