Faculty Bibliography

OBJECTIVE: Our aim in this article is 2-fold: first, to examine the mid-term to long-term data on efficacy, from controlled and naturalistic and other studies, in order to determine if they are consistent with the quantitative meta-analyses of mostly short-term, randomized controlled trials Our second (and most important) aim is to use these and other data to provide guidance about the potential relationship of these differences among antipsychotics to the individual patient's own experience with antipsychotic drugs in the process of shared decision-making with the patients and their significant others. DATA SOURCES: A search of PubMed, Embase, and PsychINFO was conducted for articles published in English between January 1, 1999, and April 2011, using the search terms double-blind AND randomized AND olanzapine AND (ziprasidone OR risperidone OR quetiapine OR haloperidol OR fluphenazine OR perphenazine OR aripiprazole). STUDY SELECTION: Studies with a duration 3 months or longer, including patients with schizophrenia or schizoaffective disorder, reporting survival analysis for all-cause discontinuation and relapse or dropout due to poor efficacy were selected. DATA EXTRACTION: We extracted the number of patients relapsed due to poor efficacy and hazard rates for relapses. DATA SYNTHESIS: Overall, the efficacy patterns of both controlled effectiveness and observational long-term studies closely parallel the efficacy observed in the short-term, controlled studies. The results of Phase 1 Clinical Antipsychotic Trials of Intervention Effectiveness are very similar to, but not identical with, the controlled short-term efficacy studies, the European First-Episode Schizophrenia Trial, and naturalistic studies. The mid-term and long-term data suggest that olanzapine is more effective than risperidone and that both of these are better than the other first- and second-generation antipsychotics except for clozapine, which is the most efficacious of all. Further large differences emerged regarding the specific mid-term and long-term safety profiles of individual antipsychotics. CONCLUSIONS: Despite intraclass differences and the complexities of antipsychotic choice, the second-generation antipsychotics are important contributions not only to the acute phase but, more importantly, to the maintenance treatment of schizophrenia.

OBJECTIVE: This study is a post hoc analysis of additions of antidepressants, anxiolytics, and sedative/hypnotics in treatment of patients randomized to antipsychotic treatment in the CATIE study, which recruited a chronic, "real world" schizophrenia sample and followed patients for up to eighteen months. We examined baseline predictors of initiation, time until initiation, and duration of treatment with antidepressants, anxiolytics, and sedative/hypnotics in CATIE study participants. METHODS: Psychotropic medication use by 1,449 CATIE study participants was documented at each study visit. Baseline demographic and clinical predictors of initiation, of time to initiation, and of duration of treatment of Concomitant Psychotropic Medications (CPMs) in each category (antidepressant, anxiolytic, and sedative/hypnotics) were identified through multiple regression analyses. RESULTS: Initiation of new CPMs post baseline by CATIE clinicians was moderately frequent, with 14.6% of patients receiving antidepressants, 13.7% receiving anxiolytics, and 11.2% receiving sedative/hypnotics. Predictors of antidepressant initiation (14.6% of group) were being female or white, and having a prior diagnosis of depression or symptoms of depression at baseline. Patients with higher positive symptom scores and younger patients were started on antidepressants sooner. Duration of antidepressant treatment was longer in patients with less education and in those with a history of alcohol abuse/dependence. Predictors of anxiolytic initiation (13.7% of group) were not being of African-American race, being separated/divorced, younger age, higher body mass index, and akathisia. Time to anxiolytic initiation was shorter in patients who were separated or divorced and in patients with better neurocognitive functioning. Duration of anxiolytic treatment was shorter for African Americans and longer in patients with better instrumental role functioning. Predictors of sedative/hypnotic use (11.2% of group) were depressive symptoms and prior diagnosis of an anxiety disorder. Time to initiation of sedative/hypnotics was longer for those with depressive symptoms and shorter for those with a history of alcohol abuse/dependence. CONCLUSIONS: Sedative/hypnotics, anxiolytics, and antidepressants were commonly used CPMs in schizophrenia during the CATIE trial, where patients were being seen frequently and antipsychotic treatment was optimized. Randomized, controlled clinical trials examining adjunctive use of antidepressants, anxiolytics and sedative/hypnotics to target symptoms of anxiety, depression, and insomnia in patients with schizophrenia are needed to adequately address the efficacy of these interventions.

At the 2008 annual meeting of the American College of Neuropsychopharmacology (ACNP), a symposium was devoted to the following question: 'what have we learned about the design of pragmatic clinical trials (PCTs) from the recent costly long-term, large-scale trials of psychiatric treatments?' in order to inform the design of future trials. In all, 10 recommendations were generated placing emphasis on (1) appropriate conduct of pragmatic trials; (2) clinical, rather than, merely statistical significance; (3) sampling from the population clinicians are called upon to treat; (4) clinical outcomes of patients, rather than, on outcome measures; (5) use of stratification, controlling, or adjusting when necessary and not otherwise; (6) appropriate consideration of site differences in multisite studies; (7) encouragement of 'post hoc' exploration to generate (not test) hypotheses; (8) precise articulation of the treatment strategy to be tested and use of the corresponding appropriate design; (9) expanded opportunity for training of researchers and reviewers in RCT principles; and (10) greater emphasis on data sharing.

Over the last 5 years, some studies have questioned the efficacy of second-generation antipsychotics over first-generation neuroleptics in the treatment of schizophrenia. At the same time, these study results have led to re-examination of their design--particularly CATIE and CUtLASS--which essentially measured relatively short-/mid-term outcome and did not always take into account real-world clinical practice and outcome measures (e.g. prevalence of positive acute symptoms, exclusion of comorbidity with substance abuse, predominance of chronic patients, lack of quality of life/wellbeing measures, etc.). In fact, one of the greatest challenges to treatment of schizophrenia is its life-long, multifaceted, functional disability associated with progressive cognitive deterioration after each acute episode. As such, the most important goal of the treatment is not just to deal with acute episodes, but rather to improve long-term outcome. Specifically, we aim for modest improvement and then stabilization of the different clinical dimensions involved in the overall symptomatology (i.e. negative/anergic, impulsive, positive, mood and cognitive impairments), and to achieve 'clinical stabilization' after obtaining a partial or full remission of acute symptoms, thus reducing the risk of a progressive cognitive deterioration. All these aspects need to be properly evaluated in a long-run perspective.

In daily practice, clinicians are interested in knowing when to expect treatment response after initiating a new antipsychotic medication. This analysis examined whether response onset and persistence can distinguish true drug from placebo responses. The methodology proposed by Quitkin et al (1984) was applied to data from three 6-week double-blind placebo-controlled trials in schizophrenia to examine response (> or =30% Positive and Negative Syndrome Scale total score reduction from baseline) here using the antipsychotic paliperidone extended release (3-12 mg/d) versus placebo. Response patterns were categorized by persistence (persistent: response at every time point from first response to end point for > or =2 time points; nonpersistent: other patterns) and onset (early: first response at day 4 to week 2; later: week 3 to end point). Persistent responses occurred in 39.8% of antipsychotic-treated patients and in 20.2% of subjects receiving placebo (P < 0.001). An early persistent response was achieved in 23.5% of those who received antipsychotic medication and by 14.2% of the subjects who received placebo, and a later persistent response was achieved in 16.3% and in 6.0%, respectively (P < 0.001 for both comparisons). A nonpersistent response occurred in 16.9% and in 18.1%, respectively (P = 0.631). No response occurred in 37.1% of the antipsychotic-treated patients and in 58.6% of the placebo-treated subjects over 6 weeks (P < 0.001). In conclusion, persistent response (occurring either early or later) is more likely achieved with antipsychotic medication than with placebo, and response patterns may be useful in assessing true drug response. Results suggest that persistent response requires continuing antipsychotic treatment beyond 2 weeks in some patients. These results may be useful for clinical decision making and patient education.

The social stigma surrounding psychiatric illness may prevent athletes from seeking counseling, psychotherapy, medication, or other treatment when needed. Few controlled studies on athletes exist to guide the team physician, clinician, or psychiatrist who must deal with diagnostic issues. Management involves setting realistic goals, educating as well as inducing the patient into treatment, soliciting support from family or significant others, and delivering appropriate treatment (the most difficult task). The objective is to improve performance and quality of life. Confidentiality issues are paramount during diagnosis and treatment. Physicians who understand sports and team dynamics may have more success in helping patients follow through with treatment.

Rapid advances in neuroscience and clinical research have made the practice of quality clinical psychopharmacology increasingly difficult. While practice guidelines, model psychopharmacology curricula, and clinical algorithms have helped "the science" of psychopharmacology, they often fail to provide guidance for clinicians in specific clinical situations with individual patients. Quality psychopharmacology practice is based on a combination of knowledge, experience, judgment, and luck. In this article, the authors present their collection of psychopharmacology "pearls" for trainees as well as experienced clinicians. (Journal of Psychiatric Practice 2009;15:423-426).

Over the past three decades, the world of both amateur and professional sports has expanded greatly and become more complex. In part related to these changes - and relatively unknown to sports medicine practitioners - the field of sport psychiatry has steadily evolved and grown. This paper focuses on what these changes have been. A sport psychiatrist is a physician-psychiatrist who diagnoses and treats problems, symptoms and/or disorders associated with an athlete, with their family/significant others, with their team, or with their sport, including spectators/fans. The primary aims of the specialty are to (i) optimize health, (ii) improve athletic performance, and (iii) manage psychiatric symptoms or disorders. The training includes medical training to provide knowledge and skills unique to physicians; psychiatric training to provide knowledge and skills inherent in that field, and training and/or experience in sport psychiatry to provide knowledge and skills about psychiatric aspects of sports. The sport psychiatrist first makes an individual, family-systems and phenomenological diagnosis of the clinical situation. Based on this evaluation, he sets goals for not only the athlete, but also for significant others involved. He delivers treatment based on the psychiatric disorder or problem using a combination of medication, psychotherapy or self-help group interventions plus strategies targeted to specific sport performance issues. Evolution of the International Society of Sport Psychiatry as well as the field, including incorporation into school and professional team sports, is described along with a 'typical day' for a sport psychiatrist. Case examples, a training curriculum and core literature are included.