L. P. Voruganti, MD, PhD

The expression "quality of life" is an intuitively familiar and popular concept, and it epitomizes the public's hopes and expectations. In clinical settings, it demands the inclusion of patients' feelings, attitudes, and opinions in medical decision making. Hence, the concept is valuable in summarizing an individual's health care needs, setting therapeutic goals, and providing client-centered holistic care. Quality of life also helps to appraise the ultimate human value of research-biological or psychosocial-through the addition of a consumer perspective. These sentiments were instrumental in propelling the recent interest in patient-reported outcomes (PRO) with quality of life as an eminent example.

It has often been quipped that quality of life is easy to understand but hard to define. At the outset, many people attempt to explain quality of life through terms such as happiness, well-being, satisfaction, or contentment. Politicians, environmentalists, and social scientists routinely use the phrase quality of life to imply a combination of material and nonmaterial well-being of communities or nations, or a cumulative index derived from measures such as gross domestic product, literacy, crime rate, green spaces, and so forth. The scope of quality of life in clinical settings is narrower and limited to assessing health determinants. Often distinguished as "health-related quality of life," the concept is defined as an individual's net satisfaction with life in the context of enduring the disabling effects of an illness on the one hand and the cumulative risks and benefits of its treatment on the other.

The 4 essential aspects of quality of life relevant to the discussion in this article can be summarized by the following questions:

• When does quality of life become relevant to clinical practice?
• How do treatment decisions affect quality of life?
• How are changes in quality of life in clinical practice tracked?
• How are pharmacological and psychosocial interventions optimally combined to enhance quality of life?

People do not view the impact of a common cold or a simple fracture in terms of quality of life but instead consider these conditions to be minor inconveniences. Similarly, researchers did not bother to study the improvement in quality of life with penicillin treatment in randomized controlled trials. Instead, assessing quality of life is relevant to clinical contexts where an illness runs a chronic course, its impact is disabling, an effective treatment is lacking, and a complete recovery is unlikely.

Schizophrenia is a prime example of this unfortunate set of circumstances.

 It is a severe, persistent mental illness that causes distress, disability, dependence, disadvantage, and, at times, premature death. Often it robs the person of individual identity and leaves the patient as a mere "schizophrenic shell." If the person with this slowly unfolding dementia praecox survives the initial stormy years and escapes the clutches of suicide, the focus shifts from the 

 of life. While the causes of this brain disorder are unclear and the effectiveness of preventive strategies remains uncertain, mental health professionals have become increasingly conscious that the effect of their eclectic interventions should, at the least, not compromise the quality of life of their patients, and, at best, should enhance it.

The focus of this article is to assess the impact of antipsychotic medications on the quality of life of individuals affected by schizophrenia.



"I am feeling a lot better. I am no longer angry and concerned about others... My concentration has come back, and I am reading books now... I am going out more on my bike, and I need to think about doing more this summer," said John, a 39-year-old man with a 15-year history of schizophrenia, on beginning his seventh month of clozapine treatment.

"I don't get the midnight panicky phone calls any more. I can spend my winter in Florida. John's quality of life is much better, and my quality of life has improved too," declared Joe, John's father, as he reclined in his chair with a big grin on his face.

"Let the rehabilitation and recovery begin in earnest," I said, looking at Angie, John's community nurse-case manager at the Wellington Psychiatric Outreach Program. It was a picture-perfect moment in community care.

Joe's reference to the improvement in quality of life was indeed a succinct expression of the multiaxial outcome of an effective intervention.


Use of antipsychotic medications remains the cornerstone of the management of schizophrenia. Despite their varied effectiveness, unpredictable response, and a range of inevitable adverse effects, the recommended strategy is to continue to give patients these medications for years (if not for the rest of their life) with the hope of avoiding the more tragic consequences of the illness. It is no wonder, therefore, that the impact of antipsychotic medications on quality of life requires closer scrutiny.



Conventional antipsychotics and quality of life

 The introduction of first-generation (conventional) antipsychotics (FGAs) is considered to be, along with psychoanalysis and the advent of community care, 1 of the 3 revolutions in the history of psychiatry. Introduced in 1955, the impact of FGAs has been felt far and wide. They were the first class of uniformly effective, relatively safe, and widely prescribed medications in the history of psychiatry. In the context of the postwar, relatively affluent, health care-focused, civil rights-oriented, liberal environment of the 1960s, these medications were quickly embraced with enthusiasm and prescribed with enormous hope. Therapy with FGAs hastened an already budding movement of deinstitutionalization and the closure of mental asylums and facilitated the growth of community care. Notions of community reintegration, independent living, and 

 were seen as realistic goals, and the opportunities for rehabilitation and recovery seemed endless.

The notion of quality of life, however, wasn't there to capture the spirit and the positive impact of FGAs. The quality of life concept had not sufficiently evolved, and the earliest measures did not become available until the late 1970s. After all, the first controlled trial involving chlorpromazine merely tracked symptomatic improvement but did not measure quality of life. However, the benefits of FGAs in preventing the long-term adverse effects of schizophrenia were established in several studies.



A quarter century of conventional antipsychotic use led to an unfolding story of disillusionment and despair. Initially touted as 

drugs, these medications were merely found to be good at suppressing symptoms and were not curative at all. A number of studies during the 1970s catalogued the disabling range of FGA-induced adverse effects, including the extrapyramidal symptoms (EPS), akathisia, dysphoria, prolac- tinemia, and tardive dyskinesia.

 The chorus of condemnation was bolstered by powerful anecdotal observations and first-person accounts.

The subjective impact of these effects was best shown by a little-known study. Bellmaker and Wald

 ingested a small dose of haloperidol and recorded their feelings. Their descriptions included "marked slowing of thinking and movement within 10 minutes, with profound inner restlessness... paralysis of volition, lack of physical and psychic energy." They were "unable to read, telephone or perform household tasks... and had to leave work for 48 hours"; they were disabled by "the feelings of severe anxiety, profound cognitive and emotional restriction." A series of later studies of people with schizophrenia systematically documented the untoward effects of FGAs and their negative impact on quality of life.

By the mid-1980s, the tide was turning against the FGAs. The therapeutic limitations of the drugs fueled by rising societal expectations (eg, focus on independent living and productivity) propelled the quest for newer and better medications. The methods for evaluating new antipsychotic drugs became more stringent, and quality of life was seen as an essential outcome measure for new clinical trials.

 Meanwhile, physicians reluctantly continued to prescribe FGAs because of the lack of a better choice.



Atypical antipsychotics and quality of life


The arrival of second-generation (atypical) antipsychotics (SGAs) in the 1990s offered choice as well as a promise of better outcomes in schizophrenia. Clinical trials suggested that SGAs might have a broader spectrum of efficacy-both in improving ancillary negative, cognitive, and depressive symptoms and in reducing the core positive psychotic symptoms. The conspicuous lack of EPS and dysphoric responses further reflected the improved subjective tolerability of these medications and the enhanced quality of life for patients.

 These original reports were later substantiated by anecdotal accounts and numerous independent, focused investigations that have been published over the past decade.



Lately, the enthusiasm surrounding the use of SGAs has been curbed by cost concerns as well as the increased risk of weight gain and metabolic aberrations. It has been estimated that the cost of SGA therapy could be 100-fold greater than that of the FGAs; and when the incremental benefits and the costs are considered together, the differences between the groups become obscured. 

Several high-profile studies, including the Cost Utility of the Latest Antipsychotics in Schizophrenia Study (CUtLASS), Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE), the Schizophrenia Outpatient Health Outcomes (SOHO) study, and the National Institute for Clinical Excellence (NICE)-commissioned health technology assessment report on atypical antipsychotic drugs, concluded that efficacy of the newer drugs is similar to or marginally better than that of their conventional counterparts; however, there aren't enough data to support the claims that the new drugs are indeed cost-effective.

In the context of the continuing debate and uncertainty about the utility and cost-effectiveness of antipsychotic drugs, quality of life remains the reference point that should direct clini- cal decisions. Prescribing practices should be guided not exclusively by research data but by each individual's needs, idiosyncratic responses, and susceptibilities to adverse effects. Clinical wisdom suggests that the class of antipsychotic drugs doesn't really matter as long as physicians remain diligent and adhere to good prescribing practices (ie, the use of minimal yet effective dosing, timely titration, monitoring of adverse effects, and assessing of individual tolerability), coupled with appropriate psychoeducation and enlistment of family support.

It is neither essential nor is it often feasible to formally assess quality of life in routine clinical practice. The choice of a drug and the decision whether to continue with the same treatment should be guided by the net impact of a medication, taking into account the magnitude of symptom control, the burden of adverse effects, subjective tolerability, and patients' reports of satisfaction with the treatment. A simplified form of the risk-benefit analysis of various psychotropic drugs is summarized in the 


There has been growing evidence to suggest that comorbidity is the rule rather than the exception among many people affected by schizophrenia. Substance abuse and anxiety disorders, especially obsessive-compulsive disorder, are common examples of psychiatric disorders that often coexist with psychotic symptoms. The quest to achieve relief from comorbid symptoms led to the unintended practice of prescribing multiple, adjunctive psychotropic medications. Benzodiazepines and antidepressants are the concurrent medications most widely used with antipsychotic medications; other common concurrent medications include antiepileptics and lithium. The clinical reality is that patients who are denied the opportunity of optimal pharmacotherapy tend to self-medicate with a range of over-the-counter medications (eg, antihistamines) or illicit drugs (eg, cannabis).

The evidence to help appraise the impact of polypharmacy, especially from a quality-of-life perspective, is still accruing and is inconclusive. While some studies show that planned, carefully monitored, targeted use of adjunctive medications offers additional relief of symptoms and enhances overall functioning and quality of life, there is a nagging concern that lapses in the continuity of care could result in inappropriate and long-term use of multiple medications as well as consequent cumulative adverse effects and impairment.



Psychosocial interventions and quality of life

 Nonpharmacological approaches are an integral part of enhancing quality of life for persons with schizophrenia. Timely introduction of psychoeducation, compliance therapy, family intervention, stress management, social skills training, and cognitive remediation techniques in suitably selected patients may complement the benefits of drug therapy and greatly enhance a patient's recovery and quality of life.




Research on quality of life has helped keep the focus on the subjective aspects of the illness experience and treatment and has identified a wide range of PROs.

 In recent years, the FDA has not only insisted on the collection of PRO data in clinical trials but it has also taken them into con- sideration in the new drug-approval process.




Enhancing quality of life is an evolving theme and a moving target. It is popular yet controversial, desirable yet demanding. Despite the potential difficulties and uncertainties, enhancing the quality of life of individuals with schizophrenia is a worthy goal for clinicians. While the conventional wisdom of 

 is a reminder of the limitations of drug therapy, the motto 

care often, cure sometimes, and comfort always

 distills the scope of enhancing quality of life in health care.



Acknowedgment-in memory of Warren Robertson.

 Lehman AF, Ward NC, Linn LS. Chronic mental patients: the quality of life issue. 

 Wyatt RJ. Neuroleptics and the natural course of schizophrenia. 

 Van Putten T, Marder SR. Behavioral toxicity of antipsychotic drugs. 

 Bellmaker RH, Wald D. Haloperidol in normals. 

 Awad AG. Subjective response to neuroleptics in schizophrenia. 

 Voruganti L, Cortese L, Ouyewumi L, et al. Comparative evaluation of conventional and new antipsychotic drugs with reference to their subjective tolerability, side effect profile and impact on quality of life.

 Voruganti L, Cortese L, Ouyewumi L, et al. Switching from conventional to novel antipsychotic drugs: results of a prospective naturalistic study. 

 Ritsner M, Gibel A, Perelroyzen G, et al. Quality of life outcomes of risperidone, olanzapine, and typical antipsychotics among schizophrenia patients treated in routine clinical practice: a naturalistic comparative study. 

 Naber D, Karow A, Lambert M. Subjective well-being under the neuroleptic treatment and its relevance for compliance. 

 Rosenheck RA. Outcomes, costs, and policy caution. A commentary on: the Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study (CUtLASS 1). 

 Revicki DA; Regulatory Issues and Patient-Reported Outcomes Task Force for the International Society for Quality of Life Research. FDA draft guidance and health-outcomes research. 

Articles

The expression "quality of life" is an intuitively familiar and popular concept, and it epitomizes the public's hopes and expectations. In clinical settings, it demands the inclusion of patients' feelings, attitudes, and opinions in medical decision making.

L. P. Voruganti, MD, PhD

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