Volume 73July 2012Number 7

Alan J Gelenberg, MD—25th Anniversary

922 A Quarter Century at the Helm [Publisher’s Note]

923 Mentor in Chief [Editorial]

Original Research

924 Relationship of Prior Antidepressant Exposure to Long-Term Prospective Outcome in Bipolar I Disorder Outpatients

Clinical Points
  • Increased prior use of antidepressants in the 18 years leading up to network entry in bipolar I disorder outpatients (mean age, 42 years) was associated with a poor long-term (≥ 6 months response) outcome to prospective naturalistic treatment.
  • The number of prior antidepressant trials (whether or not they were covered by mood stabilizers) was independently related to prospective nonresponse, as was a history of greater number of prior mood episodes and a comorbid anxiety disorder.
  • Given the emerging data on the lack of efficacy of antidepressants in bipolar depression and possible adverse effects of antidepressants on the course of the disorder described here and in the literature, it would appear advisable that other treatment options should initially be explored, and cautious use of antidepressants deferred to later in the treatment sequence.


931 Opposing Breathing Therapies for Panic Disorder: A Randomized Controlled Trial of Lowering vs Raising End-Tidal Pco2

Clinical Points
  • Breathing training designed to alter end-tidal Pco2 (partial pressure of carbon dioxide) using feedback is an efficacious treatment for panic disorder.
  • Learning to either raise or lower Pco2 was therapeutic in the current study. Respiratory theories of panic disorder were unable to predict efficacy.
  • Possible therapeutic factors common to both therapies are changed beliefs and expectancies, exposure to ominous bodily sensations, and attention to regular and slow breathing.


953 A Randomized, Double-Blind, Placebo-Controlled 8-Week Trial of the Efficacy and Tolerability of Multiple Doses of Lu AA21004 in Adults With Major Depressive Disorder

Clinical Points
  • Depressed patients demonstrated improvements on 24-Item Hamilton Depression Rating Scale and Montgomery-Asberg Depression Rating Scale total scores when treated with Lu AA21004.
  • Depressed patients with high levels of anxiety symptoms showed improvements in their depressive symptoms with Lu AA21004.
  • Improvements in depression symptoms were seen from week 2 onward for patients treated with Lu AA21004.


960 Exercise and Mental Illness: Results From the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC)

Clinical Points
  • While prescribed exercise may be helpful in managing symptoms of anxiety and depression, engagement in vigorous exercise was not associated in this cross-sectional analysis with lower rates of major depressive disorder or the anxiety disorders, indicating a more complex role of exercise in regard to these disorders than previously believed.
  • Engagement in vigorous exercise was positively associated with the incidence of bipolar disorders and substance use disorders. This association suggests that the reward-related vulnerabilities associated with these disorders, including sensation seeking and reward dependence, may also influence the pursuit of rewarding activities such as vigorous exercise.
  • Individuals with substance use disorders may have an increased affinity for the reinforcing effects of vigorous exercise, indicating that exercise might serve as a competing reward in addiction treatment.


967 The Impact of Chronic Depression on Acute and Long-Term Outcomes in a Randomized Trial Comparing Selective Serotonin Reuptake Inhibitor Monotherapy Versus Each of 2 Different Antidepressant Medication Combinations

Clinical Points
  • Evidence suggests that first-step combined antidepressant treatment does not provide a significant advantage over selective serotonin reuptake inhibitor monotherapy for patients with chronic major depressive disorder (MDD).
  • Clinicians should closely monitor patients with a history of chronic MDD to prevent early discontinuation of antidepressant treatment.
  • Patients with chronic MDD may need additional support to address the poorer treatment outcomes associated with comorbid medical and psychiatric conditions, low education and employment, and poor quality of life.


977 Maintenance of Efficacy of Lisdexamfetamine Dimesylate in Adults With Attention-Deficit/Hyperactivity Disorder: Randomized Withdrawal Design

Clinical Points
  • While the need for continued treatment of ADHD in adults is acknowledged by experienced clinicians, efficacy of stimulant treatment has not been systematically studied in a well-designed, randomized study beyond 4 to 6 weeks.
  • In adults with ADHD, discontinuation of lisdexamfetamine dimesylate after at least 6 months of stable treatment resulted in symptom relapse in 75% of participants randomized to placebo (lisdexamfetamine dimesylate withdrawal) compared with 8.9% of participants randomized to continued lisdexamfetamine dimesylate treatment; most of the relapses occurred within the first 2 weeks.
  • Adult patients with ADHD may require continued treatment; understanding the effects of continued treatment and of discontinuation may help clinicians manage patient-specific treatment options.


984 A Randomized Controlled Trial of Duloxetine Versus Placebo in the Treatment of Nonmajor Chronic Depression

Clinical Points
  • Dysthymic disorder, a form of chronic nonmajor depression, responds to a variety of antidepressant medications.
  • In this study, duloxetine, a serotonin-norepinephrine reuptake inhibitor medication, was more effective than placebo in primary outcome measures.
  • Clinicians should assess patients for chronic depression and offer treatment options including medication and psychotherapy.


1002 Agomelatine Prevents Relapse in Generalized Anxiety Disorder: A 6-Month Randomized, Double-Blind, Placebo-Controlled Discontinuation Study

Clinical Points
  • Patients with GAD maintained on agomelatine treatment of 25–50 mg/d for 6 months had a reduced risk of relapse compared to patients switched to placebo.
  • This evidence supports the view that, in clinical practice, agomelatine will have an efficacy at least equivalent to other available treatments.


1009 Are Specific Symptoms of Depression Predictive of Alzheimer’s Dementia?

Clinical Points
  • The timely co-occurrence of depression and dementia has raised the question of whether depression is a risk factor for or a prodromal feature of dementia.
  • Loss of interest is associated with later development of Alzheimer’s dementia in not-demented, not previously depressed elderly subjects.
  • Most depressive symptoms in the elderly seem to be symptoms of depression and not of prodromal Alzheimer’s dementia.


1016 Feasibility and Pilot Efficacy Results From the Multisite Cognitive Remediation in the Schizophrenia Trials Network (CRSTN) Randomized Controlled Trial

Clinical Points
  • Cognitive remediation interventions improve cognitive performance in patients with schizophrenia.
  • These interventions can be implemented at research and clinical sites without previous experience or specific expertise.
  • Clinical trials assessing the efficacy of new drugs targeting cognition in schizophrenia can feasibly use cognitive remediation to enrich the cognitive lives of patients in these trials.



1023 Can We Incorporate Psychosocial Treatment Interventions Into Psychopharmacology Clinical Trials?

Review Article

993 Psychiatric Symptoms in Systemic Lupus Erythematosus: A Systematic Review

Clinical Points
  • Depression and cognitive dysfunction are the most common psychiatric manifestations in systemic lupus erythematosus (SLE).
  • Psychiatric symptoms occur in half of SLE patients before diagnosis of their disease.
  • In female patients with new-onset depression, cognitive dysfunction, or psychosis and family history of SLE, determination of antinuclear antibody titer might help clinicians to raise the possibility of neuropsychiatric SLE.


Case Report

992 Adjunctive Oxycodone for the Treatment of Refractory Bipolar Depression

940 Pretest

CME Activity

951 Posttest


941 Adult Outcome of Attention-Deficit/Hyperactivity Disorder: A Controlled 16-Year Follow-Up Study

For Clinical Use
  • Results from this long-term follow-up study from childhood into adult life emphasize the long-term disability associated with attention-deficit/hyperactivity disorder (ADHD) in adult life, encouraging efforts at early identification and treatment of children with ADHD to help mitigate such adverse outcomes.
  • This study’s findings also emphasize the high level of persistence of neuropsychological deficits despite decline in core symptoms of ADHD.


Focus on Women’s Mental Health

1025 Gender Differences in Never-Medicated First-Episode Schizophrenia and Medicated Chronic Schizophrenia Patients

Clinical Points
  • Gender differences were compared in 262 unmedicated, first-episode schizophrenia and 960 chronic schizophrenia patients to 804 controls.
  • Chronic schizophrenia patients have notable gender differences in age at onset, smoking, symptom severity, and cognitive function, favoring women.
  • First-episode schizophrenia patients show few gender differences.


Letters to the Editor

1034 Risk Factors for Inpatient Suicide Do Not Translate Into Meaningful Risk Categories—All Psychiatric Inpatients Are High-Risk

1035 Correction

Book Reviews

1036 Psychiatry and Heart Disease: The Mind, Brain, and Heart

1037 CBT for Psychosis: A Symptom-Based Approach

1037 Pharmacotherapy of Child and Adolescent Psychiatric Disorders, 3rd ed

Online Exclusives

Practical Psychopharmacology

e889 Drugs That Escape Hepatic Metabolism [FREE to registered users]

Clinical Points
  • In certain patients, hepatic metabolism of drugs is slower or more rapid than usual; consequences include an increased risk of adverse effects or diminished treatment efficacy.
  • There are at least 5 important situations in which the hepatic metabolism of drugs is altered. These situations are briefly explained. If clinicians encounter such situations, they will need to make appropriate dose adjustments, or they can prescribe drugs that are not metabolized in the liver.
  • Important neuropsychopharmacologic agents that are not metabolized in the liver are presented and briefly discussed.


Original Research

e891 Randomized Controlled Study of the Histamine H3 Inverse Agonist MK-0249 in Adult Attention-Deficit/Hyperactivity Disorder

Clinical Points
  • Histamine is involved in the regulation of attention, and it has been hypothesized that modulation of histamine function might be a new treatment for attention-deficit/hyperactivity disorder (ADHD).
  • This hypothesis was not supported in a clinical trial in adults with ADHD using an experimental drug that modulated histamine function.
  • Future work to examine other nonstimulants with varied mechanisms of action is necessary in ADHD.


e899 Long-Term Outcome of Cognitive Impairment in Bipolar Disorder

Clinical Points
  • Neuropsychological impairment in enthymic bipolar disorder patients remains stable across time with the exception of executive measures.
  • Illness duration and subdepressive symptoms are associated with poorer performance in executive functions.
  • Early intervention strategies in bipolar disorder aiming to ameliorate cognitive dysfunctions and enhance functioning are required.


e913 Variables as Mediators or Moderators in Predicting Relapse to Any Type of Mood Episode in a Bipolar Maintenance Study

Clinical Points
  • Identification of variables as mediators or moderators is important for the prediction of relapse and may aid in the selection of specific treatments.
  • Identification of mediators and moderators may provide valuable information in the treatment planning of patients with bipolar disorder. Each mediator or moderator should also be taken into account when planning personalized treatment for bipolar disorder patients in order to reduce the risk of relapse to any mood episode.


Review Article

e906 Public and Nonprofit Funding for Research on Mental Disorders in France, the United Kingdom, and the United States

Free Online Activities

e23 Identifying and Treating Pain Caused by MS [CME]

e24 MAOIs and Depression Treatment Guidelines [CME]

Information for Authors

see www.psychiatrist.com/author.htm