Faculty Bibliography

The presence of comorbidity in major psychoses (e.g., schizophrenia and psychotic subtypes of bipolar disorder and major depressive disorder) seems to be the rule rather than the exception in both DSM-IV and ICD-10. Examining comorbidity in major psychoses, however, requires an investigation into the different levels of comorbidity (either full-blown and subsyndromal) which should be analyzed in both psychopathological and medical fields. On one hand, the high prevalence of psychiatric comorbidity in major psychoses may be the result of the current nosographic systems. On the other hand, it may stem from a common neurobiological substrate. In fact, comorbid psychopathological conditions may share a biological vulnerability, given that dysfunction in specific brain areas may be responsible for different symptoms and syndromes. The high rates of comorbidity in major psychoses require targeted pharmacological treatments in order to effectively act on both the primary diagnosis and comorbid conditions. Nevertheless, few controlled trials in comorbid major psychoses had been carried out and treatment recommendations in this field have mostly an empirical basis. The aim of the present article is to provide a comprehensive and updated overview in relation to epidemiological and clinical issues of comorbidity in major psychoses.

INTRODUCTION: In the context of a large, random assignment, controlled study evaluating the relative effectiveness and safety of antipsychotic medication (CATIE), we examined the relationship between treatment outcome and 2 family variables: their presence and their ability to support treatment adherence. METHODS: Post hoc, we assessed the 50 study patients (40 of whom had families) and their families by dividing them into 2 groups. The first had a family/significant other, available and mostly supportive, to work collaboratively on adherence with the treatment team (n = 27). The second group either did not have the family/significant other or, if they did, lacked support for long-term maintenance (n = 23). Next, we examined outcome on 2 measures: study completion (vs discontinuation) and global outcome. RESULTS: Of 27 patients with available/supportive families, 23 remained in treatment for the full study course. In contrast, 13 of 23 patients, who were discontinued or dropped out, either did not have families or, if they had them, were unable to support adherence (P < 0.01). As to global outcome, 24 of the 27 patients who had supportive families improved, compared with only 9 of the 23 of the other group (P < 0.001). DISCUSSION: In summary, in the context of a large medication efficacy-effectiveness trial, we present data suggesting that having a "family" available and supportive (regardless of the interpersonal issues between patient and family) improves outcome mediated by improving long-term adherence.

Driven by financial pressures, the sole focus of psychiatric inpatient treatment has become safety and crisis stabilization. Data are lacking on outcomes of ultrashort-stay hospitalizations; however, such stays may diminish opportunities for a sustained recovery. In the absence of an evidence base to guide clinicians and policy makers, mental health professionals have an ethical obligation to promote what they consider to be best practice. This Open Forum focuses on the need to reconsider the current model of inpatient hospitalization in order to maximize positive outcomes and emphasize appropriate transition to the community and less intensive levels of care. A model of care is presented based on rapid formulation of diagnosis, goals, and treatment modalities before treatment begins. Three phases are described--assessment, implementation, and resolution--with specific principles to guide length-of-stay decisions and requirements for staffing.

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 Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study was funded by the National Institute of Mental Health to compare the effectiveness of drugs for schizophrenia. The focus here is not on its conclusions but on the knotty issues of design and methods, in order to support appropriate clinical interpretation of the conclusions, and on using the CATIE experience to indicate directions for improvement of future clinical trials. While many of the CATIE design and implementation decisions are excellent and serve as models for future research, other decisions resulted in a study with a large study group but inadequate power. Multiple treatment interventions, unbalanced randomization within and across clinical sites, and multiple secondary outcomes are among the issues that require even more serious consideration in future large multisite clinical trials. Moreover, it is crucial to clarify whether the intent of a study is to establish superiority of some treatments or to establish equivalence, for the appropriate designs and analyses differ in these situations. If the study is designed, as was CATIE, to demonstrate some treatments' superiority, statistically nonsignificant results should not be misinterpreted as evidence of "equivalence." For establishing either superiority or equivalence, future treatment comparisons might better be designed with fewer sites, more subjects per site, fewer treatments, and fewer outcomes, in order to have the power for definitively establishing superiority or equivalence at a lower cost.

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).

OBJECTIVE: To compare the efficacy of mood stabilizer augmentation of an antipsychotic for patients with schizophrenia who are both stabilized and partially responsive. METHOD: Adult patients who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for schizophrenia or schizoaffective disorder were enrolled in a 12-week, double-blind randomized trial. Patients were stabilized on an antipsychotic, and dose remained constant. Patients were randomly assigned to 1 of 3 adjunctive treatments: (1) with lamotrigine, (2) with divalproex sodium, or (3) with placebo. Efficacy assessments included the Positive and Negative Syndrome Scale, the Calgary Depression Scale for Schizophrenia, a Demoralization Scale, and the Clinical Global Impression severity and improvement scores. The Lehman quality of life improvement scale was used to assess quality of life and social functioning. Ratings were done at each study visit, including the last visit when they had been tapered off the adjunctive treatment. RESULTS: There were no differences in global outcomes, symptoms, quality of life, or demoralization among the 3 groups. Short-term adverse effects were minimal. CONCLUSIONS: Augmenting antipsychotics with the mood stabilizers of lamotrigine or divalproex sodium for most partially responsive patients with chronic schizophrenia did not seem to be a useful treatment strategy for improving the residual symptoms. The small sample size limits firm conclusions.