How do we, as clinicians, assess the benefits and harms of any medication, including but not limited to psychiatric medications? More specifically, how do we decide whether long-term antipsychotic (AP) treatment does “more good than harm”–or vice versa, as some critics of psychiatry have claimed?
Certainly, a careful examination of the literature on relapse and remission rates in “schizophrenia spectrum” disorders** is an important part of the answer.
But we reject the notion that this is the only criterion for judging the risks and benefits of long-term AP use. Equally, we do not believe that armchair analyses of the literature by non-clinicians will answer the risk/benefit question in a humane and judicious manner.
On the contrary, we believe that the working with psychotic patients, and appreciating their often profound suffering, is an essential part of the equation.
Critics of psychiatry who have never spent time with patients and families coping with the ravages of schizophrenia simply do not grasp the human tragedy of this illness. These critics also miss the deep-seated satisfaction that comes from seeing severely impaired patients achieve remission, and even recovery—in which antipsychotic medication usually plays an important role.
As clinicians with long experience treating patients suffering with schizophrenia, our views on antipsychotic medication are shaped not only by our understanding of the scientific literature, but also by our personal care of many hundreds of patients, over several decades.
In two previous pieces, one of us (RP) examined some recent studies pointing to the benefits of long-term AP use in schizophrenia, including reduction of relapse rates and the risk of suicide.1,2 In this piece, we examine the concept of “quality of life” (QOL) and what we know about its relationship to antipsychotic use.
We focus primarily on placebo-controlled studies, despite the paucity of such investigations in the published literature.
What is Meant by “Quality of Life”?
As Berlim and Fleck noted in their 2003 review, the concept of “quality of life” is relatively new in the psychiatric literature and “embraces a whole spectrum of uses and meanings.”3
In general, however, QOL refers to “…how patients feel and how satisfied they are with treatment, besides the traditional focus on disease outcomes.”3
In 1998, the World Health Organization described QOL in these terms:
“It is a broad-ranging concept affected in a complex way by the person’s physical health, psychological state, level of independence, social relationships and their relationship to salient features of their environment.”4
Berlim and Fleck list nearly a dozen instruments or scales designed to measure QOL, including, for example, the Quality of Life Scale (QLS), the Wisconsin Quality of Life Index (W-QLI), and the Medical Outcomes Study Short Form – 36 Items (SF-36).
The main items on the original (21-item) version of the QLS5 include such factors as interpersonal relations, social initiative, work functioning, motivation, sense of purpose and emotional interaction.
QOL and Antipsychotic Medication
Bobes et al (2007)6 provide a comprehensive review of QOL in schizophrenia, based mainly on open-label and/or naturalistic studies. There were only two studies 7,8 (Hamilton et al, 1998; Nasrallah et al, 2004) comparing QOL in antipsychotic-treated patients (olanzapine or long-acting risperidone, respectively) vs. those given a placebo.
The Hamilton study evaluated patients (N=76) over a 6-month period; the Nasrallah study (N=369), over 3 months. In both studies, patients treated with the AP showed significantly greater improvement in QOL than those treated with placebo.
Indeed, Nasrallah et al found that long-acting risperidone (25 mg q 2 weeks) improved QOL to levels “not significantly different from normal,” based on the Medical Outcomes Study Short-Form 36-item questionnaire (SF-36).8
To be sure, Bobes et al acknowledge the “wide range of adverse [antipsychotic drug] effects that may negatively affect the quality of life” in patients with schizophrenia; and observe that second-generation APs may not improve QOL more than older agents. Nevertheless, the authors conclude that “….the longer the length of the illness, the worse the quality of life” and that “…the combination of psychopharmacological and psychotherapeutic treatment improve quality of life.”
The authors also observed that “…patients integrated in community support programs demonstrate a better quality of life than those who are institutionalized.”6 (Unfortunately, adequate outpatient and community supports are sadly lacking in many if not most parts of the U.S.).
One notable study not included in the Bobes et al review is that by Beasley et al (2006)9. This was a 52-week, double-blind, relapse prevention trial that tested whether stable patients with schizophrenia who were taken off active drug treatment would experience greater improvements in long-term quality of life than those who were continued on antipsychotic treatment.
The study found that, on average, Heinrichs-Carpenter Quality-of-Life Scale total scores improved by 4.3 +/- 10.6 points during treatment with olanzapine (10-20 mg/d; n = 212), but decreased by 7.1 +/- 14.6 points during treatment with placebo (n = 92; P < 0.001).
The study also found that “…stable patients with schizophrenia who were taken off active drug treatment experienced no greater improvements in long-term quality of life than those who were continued on antipsychotic treatment, even in the absence of psychotic symptoms.”9
Vothknecht et al (2011)10 studied “subjective well-being” in patients with schizophrenia, using the Subjective Well-being under Neuroleptic Treatment scale (SWN). (Subjective well-being overlaps substantially with the concept of “qualify of life”).
They reviewed open and controlled trials between 1994 and 2010, covering 44 studies. Most studies were short term (< 1 year) and none used a placebo control; rather, most compared one antipsychotic with another, with regard to improvement on the SWN.
However, six studies had a duration of one year of longer (up to three years). The key conclusion of this review was that “subjective well-being of patients with schizophrenia improved during treatment in almost all studies.”
Only a handful of placebo-controlled studies of QOL have been published since the 2007 Bobes et al paper. Leucht et al (2012)11 performed a review of all randomized trials comparing maintenance treatment with antipsychotic drugs vs. placebo, for people with schizophrenia or schizophrenia-like psychoses.
In addition to finding superiority of antipsychotic drugs compared to placebo in preventing relapse at 7-12 months, the authors found some evidence that quality of life was better in drug-treated participants (based on three randomized, controlled trials; n=527, SMD -0.62 CI -1.15 to -0.09).
Witte et al (2012)12 carried out an eight-week randomized, double-blind, placebo-controlled trial of olanzapine (long-acting injection) vs. placebo in 404 acutely ill inpatients with schizophrenia.
Four treatment arm were studied: olanzapine-LAI 210 mg/2 weeks (N = 106); olanzapine-LAI 300 mg/2 weeks (N= 100); olanzapine-LAI 405 mg/4 weeks (N= 100); and placebo (N=98). All three olanzapine-LAI treatment groups and the combined olanzapine-LAI group were superior to placebo on the QLS total score (all p-values < 0.01).
Finally, in an eight-week, randomized, placebo-controlled study of patients with acute schizophrenia, Isitt et al (2016)13 studied a new, sustained-release formulation of risperidone (RBP-7000) compared with placebo.
Patients (N=337) were assessed on health status, subjective well-being, treatment satisfaction and preference of medicine. Health-related quality of life (HRQoL) was measured using several QOL scales. The study found significantly greater improvements in HRQoL and overall well-being in patients randomized to RBP-7000 compared to placebo. Patients who received RBP-7000 also reported greater medication satisfaction on the Preference of Medicine Questionnaire (POM) compared to those on placebo.
There are certainly large gaps in our knowledge of how antipsychotic medication affects “quality of life” as compared with placebo or no medication treatment. In particular, most studies are not randomized or placebo-controlled and of those that are, most are short-term (< 1 year).
Our conclusions, therefore, must be considered provisional. Nonetheless, our review finds no support for the notion that antipsychotic medication worsens quality of life for patients with schizophrenia, and considerable controlled evidence that AP treatment improves QOL by various measures—at least within the first year of treatment, and perhaps for as long as three years (Vothknecht et al 2011)10.
Recently, Sohler et al (2015)14 reviewed studies of patients with psychotic disorders followed for at least two years, and which compared outcomes in those who received, or did not receive, antipsychotic medication during the follow-up period.
Sohler et al did not specifically study QOL; rather, they examined re-hospitalization rates, negative symptoms, positive symptoms and social functioning.
Although the authors found the evidence-base methodologically inadequate to determine the benefit-to-harm ratio of long term AP use, they did not find evidence pointing to long-term harm from APs. Specifically, they concluded, “Our study did not support the hypothesis that long-term treatment with antipsychotic medication causes harm.”
Similarly, with regard to QOL, we find no placebo- controlled evidence that use of APs for up to one year causes any decline in quality of life; indeed, the studies we reviewed show that AP treatment typically enhances QOL for patients with schizophrenia. That said, it is clear that we need more long-term (>1 year), placebo-controlled studies of QOL and its relationship to antipsychotic treatment.
The decision to continue antipsychotic medication for the long-term requires more than a survey of the research literature. It is a decision based, among other considerations, on the particular patient’s history; risk factors; response to initial treatment; side effect burden; and perhaps most importantly, the degree of suffering and incapacity the patient has endured, as a consequence of having schizophrenia.
Thus, careful assessment of the patient’s quality of life should also be a part of the decision-making process, which should involve active and respectful collaboration with the patient (and sometimes, the patient’s family). An ongoing process of informed consent and periodic monitoring of the patient’s response to treatment is essential.
The decision regarding long-term treatment should not be a binary “either/or” choice; rather, the goal should be to find the best medication and dose, with the least side effects, for the particular patient. For some carefully selected patients with schizophrenia—and in most cases of “brief psychotic disorder”15–a slow tapering and discontinuation of antipsychotic medication may be warranted, with close monitoring of the patient’s response.
In our view, when non-clinician critics argue that most patients with schizophrenia would be “better off” without long-term antipsychotic medication—or that antipsychotics have done more harm than good–they are misinterpreting the best available evidence.
Moreover, patients who impulsively discontinue their medication on the basis of such misinformation are jeopardizing their health, safety, and quality of life.16 Our review suggests that, amidst the shrill rhetoric of anti-psychiatry, the voices of patients who have done well on antipsychotic medication often go unheard.
**We use the term “schizophrenia” in the syndromal sense; i.e., we recognize that the DSM-5 construct of schizophrenia most likely represents a “final common pathway” with several different etiologies; that there is probably a “spectrum” of schizophrenia-like conditions; and that the genetics and pathophysiology of schizophrenia probably overlap with other types of psychotic illness. The treatment of these conditions must be individualized, including decisions concerning the use of long-acting antipsychotic medication.
Ronald W. Pies MD is Professor of Psychiatry and Lecturer on Bioethics at SUNY Upstate Medical University; Clinical Professor of Psychiatry, Tufts University School of Medicine; and Editor-in-Chief Emeritus of Psychiatric Times.
Joseph M. Pierre MD is Associate Director of Residency Education, UCLA Semel Institute for Neuroscience & West Los Angeles VA Medical Center; Acting Chief, Inpatient Psychiatry, West Los Angeles VA Medical Center; and Health Sciences Clinical Professor, Department of Psychiatry & Biobehavioral Sciences, David Geffen School of Medicine at UCLA.
1. Pies R: “How Antipsychotic Medication May Save Lives”
- Pies R: Long-term Antipsychotic Treatment: Effective and Often Necessary, with Caveats http://www.psychiatrictimes.com/blogs/long-term-antipsychotic-treatment-effective-and-often-necessary-caveats
- Berlim MT, Fleck MPA: Quality of life: presentation of the concept. Rev Bras Psiquiatr 2003;25(4):249-52
- The WHOQOL Group. The World Health Organization Quality of Life Assessment (WHOQOL): development and general psychometric properties. Soc Sci Med 1998;46:1569-85.
- Heinrichs DW, Hanlon TE, Carpenter WT Jr. The Quality of Life Scale: an instrument for rating the schizophrenic deficit syndrome. Schizophr Bull. 1984;10(3):388-98.
- Bobes J, Garcia-Portilla MP, Bascaran MT et al:Quality of life in schizophrenic patients. Dialogues Clin Neurosci. 2007;9(2):215-26. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181847/
- Hamilton SH, Revicki DA, Genduso LA, Beasley CM. Olanzapine versus placebo and haloperidol: quality of life and efficacy results of the North American double-blind trial. Neuropsychopharmacology. 1998;18:41-49.
- Nasrallah HA, Duchesne I, Mehnert A et al: Health-related quality of life in patients with schizophrenia during treatment with long-acting, injectable risperidone. J Clin Psychiatry. 2004;65:531-536.
- Beasley CM Jr, Sutton VK, Taylor CC et al: Is quality of life among minimally symptomatic patients with schizophrenia better following withdrawal or continuation of antipsychotic treatment? J Clin Psychopharmacol. 2006 Feb;26(1):40-4.
- Vothknecht S, Schoevers RA, de Haan L. Subjective well-being in schizophrenia as measured with the Subjective Well-Being under Neuroleptic Treatment scale: a review. Aust N Z J Psychiatry. 2011 Mar;45(3):182-92.
- Leucht S, Tardy M, Komossa K, et al: Maintenance treatment with antipsychotic drugs for schizophrenia. Cochrane Database Syst Rev. 2012 May 16;(5):CD008016.
- Witte MM, Case MG, Schuh KJ, et al. Effects of olanzapine long-acting injection on levels of functioning among acutely ill patients with schizophrenia. Curr Med Res Opin. 2012 Mar;28(3):315-23. doi: 10.1185/03007995.2012.657300. Epub 2012 Jan 31.
- Isitt JJ, Nadipelli VR, Kouassi A et al: Health-related quality of life in acute schizophrenia patients treated with RBP-7000 once monthly risperidone: An 8-week, randomized, double-blind, placebo-controlled, multicenter phase 3 study. Schizophr Res. 2016 Jul;174(1-3):126-313
- 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.
- Memon MA: Brief Psychotic Disorder http://emedicine.medscape.com/article/294416-overview
- Frances A: Setting the Record Straight on Antipsychotics http://www.huffingtonpost.com/allen-frances/setting-the-record-straig_23_b_9243828.html
For Further Reading:
Staring AB, Mulder CL, Duivenvoorden HJ et al: Fewer symptoms vs. more side-effects in schizophrenia? Opposing pathways between antipsychotic medication compliance and quality of life. Schizophr Res. 2009 Aug;113(1):27-33
Cortesi PA, Mencacci C, Luigi F, et al: Compliance, persistence, costs and quality of life in young patients treated with antipsychotic drugs: results from the COMETA study. BMC Psychiatry. 2013 Mar 22;13:98.
Strakowski SM, Johnson JL, Delbello MP, et al: HGDH Research Group. Quality of life during treatment with haloperidol or olanzapine in the year following a first psychotic episode. Schizophr Res. 2005;78(2–3):161–169
Pies R: Trivializing the suffering of psychosis. Psychiatric Times. Dec. 22, 2014. http://www.psychiatrictimes.com/schizophrenia/trivializing-suffering-psychosis