Revisiting the 'self-medication' hypothesis in light of the new data linking low striatal dopamine to comorbid addictive behavior.

Persons with schizophrenia are at a high risk, almost 4.6 times more likely, of having drug abuse problems than persons without psychiatric illness. Among the influential proposals to explain such a high comorbidity rate, the 'self-medication hypothesis' proposed that persons with schizophrenia take to drugs in an effort to cope with the illness and medication side effects.

The impact of newer atypical antipsychotics on patient-reported outcomes in schizophrenia.

Over the past two decades there has been increasing interest in including patients' self-reports in the management of their illness. Among the many reasons for such recent interest has been a rising consumer movement over the past few decades, which has led patients, their caregivers and their families to press for more meaningful sharing with physicians in the clinical decision-making process, with the clear expectations of better therapies and improved outcomes. Patients as consumers of services, their views, attitudes towards healthcare, as well as their level of satisfaction with care, have become increasingly recognized.

Measuring quality of life in patients with schizophrenia: an update.

In 1997, we published a review in PharmacoEconomics about quality of life (QOL) measurement in patients with schizophrenia. The objective of this article is to provide an update, as well as to revisit the development of the construct of QOL and its measurement as applied to schizophrenia. Since our previous article, there has been significant growth in the number of publications about QOL in schizophrenia.

Diabetes mellitus during pregnancy and increased risk of schizophrenia in offspring: a review of the evidence and putative mechanisms.

Objective: To identify converging themes from the neurodevelopmental hypothesis of schizophrenia and the pathophysiology of diabetic pregnancy and to examine mechanisms by which diabetes mellitus in a pregnant mother may increase the risk of schizophrenia in offspring.

Methods: We reviewed relevant publications on clinical, epidemiologic and animal studies of diabetic pregnancy and the neurodevelopmental aspects of schizophrenia.

Results: Epidemiologic studies have shown that the offspring of mothers who experienced diabetes mellitus during their pregnancies are 7 times more likely to develop schizophrenia, compared with those who were not exposed to diabetic pregnancy.

Insulin, insulin-like growth factors and incretins: neural homeostatic regulators and treatment opportunities.

Mood disorders may be conceptualized as progressive neurodegenerative disorders associated with cognitive decline. Novel treatments capable of preserving and/or enhancing cognitive function represent an area of priority for research in the future. Insulin, insulin-like growth factor (IGF)-1 and incretins may play a critical role in both physiological and pathophysiological processes of the CNS.

New generation antipsychotic drugs and compliance behaviour.

Purpose Of Review: Antipsychotic therapy has been eclipsed by high rates of noncompliance; the problem was attributed to a lack of efficacy and the burden of side effects of neuroleptics. This review sought to examine whether the arrival of second generation (atypical) antipsychotic drugs with low side-effect liability and improved efficacy has helped to positively reinforce compliance behaviour among people treated for schizophrenia.

Recent Findings: The number of studies that systematically examined compliance behaviour and its determinants during antipsychotic drug therapy is disappointingly low.

The burden of schizophrenia on caregivers: a review.

Schizophrenia is a disabling, chronic psychiatric disorder that poses numerous challenges in its management and consequences. It extols a significant cost to the patient in terms of personal suffering, on the caregiver as a result of the shift of burden of care from hospital to families, and on society at large in terms of significant direct and indirect costs that include frequent hospitalizations and the need for long-term psychosocial and economic support, as well as life-time lost productivity. 'Burden of care' is a complex construct that challenges simple definition, and is frequently criticized for being broad and generally negative.

Dysglycemia in a community sample of people treated for schizophrenia: the Diabetes in Schizophrenia in Central-South Ontario (DiSCO) study.

Objective: Despite increasing recognition of schizophrenia as a risk factor for diabetes, the prevalence and correlates of dysglycemia in people with schizophrenia have not been adequately studied. Discerning the modifiable risk factors is crucial for developing diabetes prevention strategies in schizophrenia.

Methods: Socio-demographic, clinical and recent laboratory data were compiled from the case records and supplemental sources of 1123 people treated for schizophrenia who were living across five different communities in the region.

Cognition, functioning and quality of life in schizophrenia treatment: results of a one-year randomized controlled trial of olanzapine and quetiapine.

Background: Cognitive deficits are recognized as a critical determinant of functional outcomes in schizophrenia; and second generation antipsychotic drugs have been touted for their potential to enhance cognitive functioning and community tenure.

Objectives: The study examined the relative merits of olanzapine and quetiapine in improving cognitive deficits and enhancing psychosocial functioning in a sample of community dwelling adults previously treated with first generation antipsychotic drugs for schizophrenia.

Methods: In a prospective, rater-blinded study, 86 participants were randomized to receive either olanzapine or quetiapine, and assessed at baseline and after 3, 6, 9 and 12 months.

Going beyond: an adventure- and recreation-based group intervention promotes well-being and weight loss in schizophrenia.

Objective: To undertake a preliminary study to assess the feasibility of clinical implementation and evaluate the effectiveness of a novel adventure- and recreation-based group intervention in the rehabilitation of individuals with schizophrenia.

Methods: In a 2-year, prospective, case-control study, 23 consecutively referred, clinically stabilized schizophrenia patients received the new intervention over an 8-month period; 31 patients on the wait list, considered the control group, received standard clinical care that included some recreational activities. Symptom severity, self-esteem, self-appraised cognitive abilities, and functioning were documented for both groups with standardized rating scales administered at baseline, on completion of treatment, and at 12 months posttreatment.

Subjective and behavioural consequences of striatal dopamine depletion in schizophrenia--findings from an in vivo SPECT study.

Dysphoria is an integral part of the symptomatology of a variety of clinical states, though there is little empirical data available on the qualitative and quantitative aspects of this phenomenon. The purpose of the study was to administer alphamethyl paratyrosine (AMPT), a catecholamine depleting agent as a chemical probe to induce dysphoria, and document the ensuing changes in mental status. AMPT (4-5 g/day) was administered to a group of medication-free schizophrenic patients (n=13) over a 48 hour period, and changes in their mental status were monitored at 12 hour intervals with the Profile of Mood States (POMS), Addiction Research Center Inventory (ARCI), Drug Attitude Inventory (DAI) and other standardized rating scales.

Brain imaging research on subjective responses to psychotropic drugs.

Objective: Neuroimaging studies on subjective responses to psychotropic drugs in humans were reviewed to examine progress in the field and identify gaps in knowledge.

Method: An exhaustive search of computerized databases identified two categories of in vivo imaging studies: i) correlates of negative(dysphoric) subjective responses to neuroleptic use in schizophrenia, and ii) research on positive (euphoric) subjective responses, mostly from substance abuse population.

Results: Research has been largely confined to neurochemical imaging of dopamine in the striatal complex, confirming earlier speculations that impaired or deficient dopaminergic function is associated with dysphoric responses, and enhanced activity is associated with euphoric or pleasurable responses.

Neuroleptic dysphoria: revisiting the concept 50 years later.

Objective: To review the concept of neuroleptic dysphoria, its historical development and the current state of the art.

Method: This paper is based on extensive but selective literature review and also draws on our extensive clinical and research experiences.

Results: Although the construct of neuroleptic dysphoria was recognized shortly following the introduction of the first antipsychotic, chlorpromazine, it took several years for the concept to receive adequate research and clinical attention.

Impact of atypical antipsychotics on quality of life in patients with schizophrenia.

Schizophrenia is a long-term disabling illness that affects approximately 1% of the population. Its course is generally chronic with acute psychotic exacerbations that may require frequent hospitalisations. The clinical picture includes a range of symptoms such as delusions, hallucinations, agitation, suspiciousness, hostility, conceptual disorganisation, blunted affect, emotional and social withdrawal, lack of spontaneity, poverty of speech and a wide range of neurocognitive deficits.

Body weight, image and self-esteem evaluation questionnaire: development and validation of a new scale.

This report describes the development of a new questionnaire designed to capture and quantify the psychosocial impact of weight gain associated with psychotropic drug use, and presents results of a preliminary validation study. Based on a review of literature, consultations with experts, interviews with individual patients and focus groups, themes relevant to weight gain and its psychosocial consequences were identified. A 12-item self-report questionnaire was designed and administered to a heterogeneous group of psychiatric outpatients (n = 141) receiving antipsychotic and other adjunctive medications.

New antipsychotics, compliance, quality of life, and subjective tolerability--are patients better off?

Objectives: This overview reviews the impact of second-generation antipsychotics on less frequently researched outcomes such as medication-adherence behaviour, quality of life, and subjective tolerability in patients with schizophrenia.

Methods: We selectively reviewed recent literature and considered our own research and experiences in the field.

Results: Most published studies about second-generation antipsychotics have dealt with issues related to efficacy and safety.

Is neuroleptic dysphoria a variant of drug-induced extrapyramidal side effects?

Objectives: Neuroleptic drugs induce psychological side effects such as dysphoria, cognitive impairment, and loss of motivation. These side effects were largely underrecognized and trivialized in the past as variants of extrapyramidal side effects (EPSEs). We review the recent literature on the subject and clarify the relation between neuroleptic-induced dysphoria and EPSEs.

Neuroleptic dysphoria: towards a new synthesis.

Rationale: Neuroleptic dysphoria (ND) is a subtle and under-recognized side effect of antipsychotic drugs. It is an all-inclusive descriptive phrase that encompasses a variety of unpleasant subjective changes in arousal, mood, thinking and motivation induced by neuroleptic drugs. Understanding this phenomenon has wide ranging clinical and research implications.

An evaluation of a stress management program for individuals with schizophrenia.

Vulnerability-stress models suggest that training in specific stress management techniques should yield benefits to those suffering from schizophrenia and related disorders. In this paper, we describe an evaluation of the impact of adding a stress management program to other medical and psychosocial interventions for such patients. Outcomes were compared for 121 patients randomly assigned to receive either a 12-week stress management program with follow-up sessions or participation in a social activities group.

Switching from conventional to novel antipsychotic drugs: results of a prospective naturalistic study.

Objective: We examined the long-term consequences of switching patients from conventional to novel antipsychotic drugs, from a patient's perspective.

Methods: In a prospective, single-blinded, naturalistic study, a cohort of subjects (n=150) with schizophrenia or schizo-affective disorder (DSM-IV) were switched from conventional neuroleptic drugs to either risperidone (n=50), olanzepine (n=50) or quetiapine (n=50), and monitored for a period of 2 to 6 years. The ensuing natural history of transitions in treatments was charted, and the outcomes including symptoms, side effects, subjective tolerability of drugs and their impact on quality of life were documented with standardized rating scales.

Personal evaluation of transitions in treatment (PETiT):a scale to measure subjective aspects of antipsychotic drug therapy in schizophrenia.

The paper describes the development and preliminary testing of a scale designed to capture aspects of subjective responses to, and tolerability of antipsychotic drugs, treatment adherence, and impact of antipsychotic drug therapy on the quality of life of individuals treated for schizophrenia. Using empirical study approaches and qualitative methods of data analysis, twelve themes were initially identified as relevant to the quality of life of individuals during antipsychotic drug therapy. Based on these dimensions, in the second phase, a 30 item self report questionnaire was constructed and field tested in a community based, heterogeneous sample of schizophrenic patients (n=335).

What's in a name? The evolution of the nomenclature of antipsychotic drugs.

Objective: Psychiatry as a science and psychotherapy as an art thrive on words, words that were often coined arbitrarily and that are often used idiosyncratically. This article examines the origins, progenitors and usage of the word "antipsychotic" and explores its ramifications.

Methods: Original publications from the 1950s onward, beginning with the report of the discovery of chlorpromazine, were sought for their specific references to the terminology of drugs used to treat psychotic disorders.

Subjective effects of AMPT-induced dopamine depletion in schizophrenia: correlation between dysphoric responses and striatal D(2) binding ratios on SPECT imaging.

Approximately one third of schizophrenic patients treated with neuroleptic drugs experience unpleasant subjective responses, that are collectively known as neuroleptic dysphoria. Experimental research in animals indicates that drug induced dopaminergic blockade in mesolimbic circuits, especially the nucleus accumbens, leads to impaired pleasure responsivity and dysphoria. The present study tested this putative mechanism in drug-free schizophrenic patients (n = 12), through inducing dysphoric responses with alphamethyl paratyrosine (AMPT) and simultaneously quantifying their baseline striatal dopmine (D(2)) function with (123)IBZM-SPECT imaging.

Cannabis induced dopamine release: an in-vivo SPECT study.

In a research study aimed at examining the alterations in dopaminergic function in schizophrenia, the authors identified a surreptitious case scenario which provided new insights into the subjective and neurochemical effects of cannabis. A 38-year-old drug-free schizophrenic patient took part in a single photon emission computerized tomographic (SPECT) study of the brain, and smoked cannabis secretively during a pause in the course of an imaging session. Cannabis had an immediate calming effect, followed by a worsening of psychotic symptoms a few hours later.