February 2014

Vol. 26. No. 1


A view from the ground

I’ve been thinking about mental health care and the Affordable Care Act (ACA) and want to blow off some steam. I am hoping that over time our patients will experience less stigma, that the ACA will help bring parity to mental illnesses with regard to insurance coverage and that access to psychiatric care will improve…



Extended-release quetiapine fumarate (quetiapine XR) as adjunctive therapy in patients with generalized anxiety disorder and a history of inadequate treatment response: A randomized, double-blind study

Arifulla Khan, MD | Sarah Atkinson, MD | Irina Mezhebovsky, MD | Fahua She, MS | Todd Leathers, MBA | Sanjeev Pathak, MD

BACKGROUND: For many patients with generalized anxiety disorder (GAD), first-line treatment does not lead to remission. This study investigated the efficacy and tolerability of adjunctive extended-release quetiapine fumarate (quetiapine XR) in patients with GAD and an inadequate response to discerning serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs).

METHODS: Patients were randomized to quetiapine XR or placebo adjunctive to SSRI/SNRIs in an 11-week study. The primary endpoint was change from randomization to week 8 in Hamilton Anxiety Rating Scale (HAM-A) total score. Secondary variables were HAM-A psychic/somatic clusters, response, and remission, and Clinical Global Impression–Severity of Illness (CGI-S) score.

RESULTS: A total of 409 patients received quetiapine XR (n = 209) or placebo (n = 200). The week 8 mean change in HAM-A total score was not statistically significant for quetiapine XR (–10.74; P = .079) vs placebo (–9.61). Secondary variables were generally consistent with the primary analysis, except for a significant reduction in HAM-A total score (week 1) and significant improvements in HAM-A psychic cluster and CGI-S total scores (week 8). Adverse events included dry mouth, somnolence, sedation, headache, and dizziness.

CONCLUSIONS: In patients with GAD and an inadequate response to SSRI/ SNRIs, adjunctive quetiapine XR did not show a statistically significant effect for the primary endpoint at week 8, although some secondary endpoints were statistically significant vs placebo. Quetiapine XR was generally well tolerated.


Impact of exogenous testosterone on mood: A systematic review and meta-analysis of randomized placebo-controlled trials

Hamid R. Amanatkar, MD | John T. Chibnall, PhD | Byung-Woun Seo, PhD | Jothika N. Manepalli, MD | George T. Grossberg, MD

BACKGROUND: In the last decade, there has been a surge of new clinical trials studying the impact of exogenous testosterone on mood. The results of these studies have been inconsistent.

METHODS: Meta-analysis of controlled clinical trials using common depression rating scales was performed.

RESULTS: Sixteen trials with a total of 944 subjects met selection criteria. Meta-analysis of data showed a significant positive impact of testosterone on mood (z = 4.592; P < .0001). Subgroup analysis showed a significant effect size of 5.279 (P < .0001) in the trials with a mean age of <60 years. However, the effect size was not statistically significant in those trials with a mean age of >60 years. The effect size in hypogonadal men was 4.192 (P < .0001), whereas the result was not statistically significant in eugonadal men. In addition, the effect size was larger in subthreshold depression compared with major depression. Oral testosterone compared with oral dehydroepiandrosterone, testosterone gel, and intramuscular testosterone did not show a significant result. Larger effect size was observed in the studies of 8 to 24 weeks’ duration.

CONCLUSIONS: Testosterone may be used as a monotherapy in dysthymia and minor depression or as an augmentation therapy in major depression in middle-aged hypogonadal men.


Barriers to utilizing long-acting injectable antipsychotic medications

Hayley Getzen, MPH | Marie Beasley, DO | Dale A. D’Mello, MD

BACKGROUND: Long-acting injectable (LAI) antipsychotic medications are superior to their oral equivalents in reducing relapse, yet schizophrenia treatment guidelines favor oral formulations. A minority of eligible patients receive LAI preparations in the United States. The purpose of the present study is to examine barriers faced by psychiatrists in implementing the use of LAI antipsychotics.

METHODS: An internet survey sent to Michigan State University-affiliated psychiatrists examined psychiatrists’ practice locations and characteristics, access, opinions, and barriers to utilizing LAI antipsychotic medications in patients with schizophrenia. Thirty-six psychiatrists completed the survey.

RESULTS: Thirty-three psychiatrists (83%) acknowledged having patients in their practices who would benefit from LAI antipsychotics; however, only 22 (61%) had the capacity to utilize these formulations. Barriers to utilizing LAI antipsychotic medications included: 1) lack of ancillary support at the practice location; 2) personal preference for oral compounds; and 3) limited insurance coverage. Psychiatrists who had the capability of administering LAI antipsychotic compounds were 10 times more likely to utilize them when compared with others who lacked the capacity to do so (9.67% [SD = 10] vs 1.43% [SD = 3]; df = 1; F = 8.59; P < .005).

CONCLUSIONS: Psychiatrists practicing in Michigan face formidable barriers to utilizing LAI agents. Strategies to mitigate these barriers are reviewed.


Excluding the typical patient: Thirty years of pharmacotherapy efficacy trials for obsessive-compulsive disorder

Brian L. Odlaug, PhD, MPH | Eric Weinhandl, MS | Maria C. Mancebo, PhD | Erik L. Mortensen, MSc | Jane L. Eisen, MD | Steven A. Rasmussen, MD | Liana R. N. Schreiber, BA | Jon E. Grant, JD, MD, MPH

BACKGROUND: Over the past 30 years, clinical trials have resulted in several successful pharmacotherapies for obsessive-compulsive disorder (OCD), yet patients in clinical settings often report inadequate response. This study compares clinical characteristics of treatment-seeking OCD patients to the inclusion/exclusion criteria used in pharmacotherapy trials.

METHODS: The sample consisted of 325 community members with a DSM-IV diagnosis of OCD who underwent systematic interviews with clinicians knowledgeable in the diagnosis and treatment of OCD. We compiled pharmacotherapy studies for OCD published between 1980 and 2010 using Medline, PubMed, and library resources, and estimated the proportion of patients in each decade satisfying the most common inclusion/ exclusion criteria.

RESULTS: We included 39 clinical trials and found 72% of the 325 patients would have been excluded from trials conducted between 1980 and 2010. Exclusion was projected as dramatically lower for trials conducted between 1980 and 1989 (19.7%) compared with 74.8% for trials conducted between 1990 and 1999 and 76.9% for trials between 2000 and 2010.

CONCLUSIONS: The majority of treatment-seeking individuals with OCD would not qualify for OCD treatment studies due to comorbid psychiatric disorders, and failure to meet OCD severity threshold criteria. This illustrates the need to include a more community representative sample of OCD patients in clinical trials examining pharmacotherapy efficacy.