Recently, the blogosphere has been buzzing with controversy about maintenance antipsychotic treatment.1,2 On the one hand, most psychiatrists who have treated severely impaired patients with schizophrenia have little doubt that long-term antipsychotic treatment is both effective and necessary to avoid relapse of psychotic illness. On the other hand, a few recent studies seem to cast doubt on this belief, and a number of psychiatry’s critics have seized on these studies to argue against long-term antipsychotic use—even declaring that in the long run antipsychotics worsen psychosis and clinical outcome for those with schizophrenia.1,2
This article is by no means a comprehensive review of the voluminous, decades-old literature on antipsychotic maintenance; rather, it is a commentary on some recent studies and their sometimes controversial interpretation. I would argue that interpreting these complex studies requires an in-depth understanding of medical research design, psychopharmacology, and the numerous confounding factors that can affect treatment outcome. Unfortunately, a lack of medical training has not stopped a few critics from confidently charging that psychiatrists are harming their patients by prescribing long-term antipsychotic treatment.1,2
What does the recent literature say?
We need to make modest claims—not sweeping generalizations—about the literature on long-term use of antipsychotic medication. “Gold-standard,” randomized, placebo-controlled studies are fewer than we would like, and existing studies are always subject to different interpretations.
Nonetheless—to prefigure my main arguments—I believe that most randomized, long-term studies of schizophrenia support the net benefit of antipsychotics in preventing relapse of the illness. Some data also show better “quality of life” with maintenance antipsychotic treatment, compared with drug discontinuation. There is no convincing evidence that maintenance treatment causes worsening of schizophrenia or related psychotic illnesses or leads to poorer outcomes, when compared with discontinuation of the antipsychotic.
That said, data from Dr Lex Wunderink and colleagues3 suggested to some that long-term antipsychotic treatment may do more harm than good. Essentially, these researchers compared rates of recovery in patients with remitted first-episode psychosis after 7 years of follow-up of a dose reduction/discontinuation versus maintenance treatment trial. After 6 months of remission, patients were randomly assigned to a dose reduction/discontinuation strategy or maintenance treatment for 18 months. After the trial, treatment was at the discretion of the clinician.
The primary outcome was rate of recovery, defined as meeting the criteria of symptomatic and functional remission. At the 18-month mark, dose reduction/discontinuation resulted in significantly greater relapse rates compared with medication maintenance, as many psychiatrists would have expected. However, at 7 years, the dose reduction/discontinuation group showed unexpectedly higher recovery rates than the maintenance treatment group—40.4% versus 17.6%. This finding seemed to suggest that long-term antipsychotic maintenance worsened outcome after first-episode psychosis.
But as schizophrenia specialist Dr Joseph M. Pierre2 has pointed out, this conclusion is unwarranted. First of all, most of the subjects in the dose reduction/discontinuation arm of the study actually remained on antipsychotic medication, although at a reduced dose. Second, as Dr Pierre notes, “. . . while the initial treatment group allocation was randomized, the subsequent dose changes in both treatment groups were based on clinical response and occurred at the whim of the treating psychiatrists.”2 Thus, this was not really a randomized study. And rather than antipsychotic treatment worsening outcome, it seems more likely that patients perceived by their doctors as doing relatively well were, understandably, given lower doses of medication. Conversely, patients perceived as doing worse were likely maintained on higher doses.
1. Frances A. Do antipsychotics help or harm psychotic symptoms? Psychol Today. February 1, 2016. https://www.psychologytoday.com/blog/saving-normal/201602/do-antipsychot.... Accessed February 22, 2016.
2. Pierre J. Do antipsychotics worsen schizophrenia in the long-run? Psychol Today. August 8, 2014. https://www.psychologytoday.com/blog/psych-unseen/201408/do-antipsychoti.... Accessed February 22, 2016.
3. Wunderink L, Nieboer RM, Wiersma D, et al. Recovery in remitted first-episode psychosis at 7 years of follow-up of an early dose reduction/discontinuation or maintenance treatment strategy: long-term follow-up of a 2-year randomized clinical trial. JAMA Psychiatry. 2013;70:913-920.
4. Mayoral-van Son J, Ortiz-Garcia de la Foz V, Martinez-Garcia O, et al. Clinical outcome after antipsychotic treatment discontinuation in functionally recovered first-episode nonaffective psychosis individuals: a 3-year naturalistic follow-up study. J Clin Psychiatry. 2015 Dec 8. [Epub ahead of print].
5. Harrow M, Jobe TH, Faull RN. Does treatment of schizophrenia with antipsychotic medications eliminate or reduce psychosis? A 20-year multi-follow-up study. Psychol Med. 2014;44:3007-3016.
6. Sohler N, Adams BG, Barnes DM, et al. Weighing the evidence for harm from long-term treatment with antipsychotic medications: a systematic review. Am J Orthopsychiatry. 2015 Dec 14. [Epub ahead of print].
7. Leucht S, Tardy M, Komossa K, et al. Maintenance treatment with antipsychotic drugs for schizophrenia. Cochrane Database Syst Rev. 2012;5:CD008016.
8. Ran MS, Weng X, Chan CL, et al. Different outcomes of never-treated and treated patients with schizophrenia: 14-year follow-up study in rural China. Br J Psychiatry. 2015;207:495-500.
9. Venkatasubramanian G. Neuroanatomical correlates of psychopathology in antipsychotic-naïve schizophrenia. Indian J Psychiatry. 2010;52:28-36.
10. Lesh TA, Tanase C, Geib BR, et al. A multimodal analysis of antipsychotic effects on brain structure and function in first-episode schizophrenia. JAMA Psychiatry. 2015;72:226-234.
11. Gellad WF, Aspinall SL, Handler SM, et al. Use of antipsychotics among older residents in VA nursing homes. Med Care. 2012;50:954-960.
12. Tiihonen J, Mittendorfer-Rutz E, Torniainen M, et al. Mortality and cumulative exposure to antipsychotics, antidepressants, and benzodiazepines in patients with schizophrenia: an observational follow-up study. Am J Psychiatry. 2015 Dec 7. [Epub ahead of print]. http://ajp.psychiatryonline.org/doi/abs/10.1176/appi.ajp.2015.15050618. Accessed February 22, 2016.