Thirty years of clinical experience with carbamazepine in the treatment of bipolar illness: principles and practice.

Carbamazepine began to be studied in a systematic fashion in the 1970s and became more widely used in the treatment of bipolar disorder in the 1980s. Interest in carbamazepine has been renewed by (i) the recent US FDA approval of a long-acting preparation for the treatment of acute mania; (ii) studies suggesting some efficacy in bipolar depression; and (iii) evidence of prophylactic efficacy in some difficult-to-treat subtypes of bipolar illness. A series of double-blind controlled studies of the drug were conducted at the US National Institute of Mental Health from the mid-1970s to the mid-1990s. This review summarises our experience in the context of the current literature on the clinical efficacy, adverse effects and pharmacokinetic interactions of carbamazepine. Carbamazepine has an important and still evolving place in the treatment of acute mania and long-term prophylaxis. It may be useful in individuals with symptoms that are not responsive to other treatments and in some subtypes of bipolar disorder that are not typically responsive to a more traditional agent such as lithium. These subtypes might include those patients with bipolar II disorder, dysphoric mania, substance abuse co-morbidity, mood incongruent delusions, and a negative family history of bipolar illness in first-degree relatives. In addition, carbamazepine may be useful in patients who do not adequately tolerate other interventions as a result of adverse effects, such as weight gain, tremor, diabetes insipidus or polycystic ovarian syndrome. We review our clinical and research experience with carbamazepine alone and in combination with lithium, valproic acid and other agents in complex combination treatment of bipolar illness. More precise clinical and biological predictors and correlates of individual clinical responsiveness to carbamazepine and other mood stabilisers are eagerly awaited.

The use of antiepileptic drugs in bipolar disorders: a review based on evidence from controlled trials.

Antiepileptic drugs (AEDs) have diverse psychotropic profiles. Some AEDs have proven to be efficacious in the treatment of mood disorders, especially bipolar disorder. Others are ineffective as primary treatments but may be useful adjuncts for mood disorders or comorbid conditions. Valproate (acute mania and mixed episodes), carbamazepine (acute mania and mixed episodes), and lamotrigine (maintenance to delay recurrence) have United States Food and Drug Administration indications for the treatment of bipolar disorder. This article provides an overview of data on the use of AEDs in bipolar disorder, including acute mania and depression, prophylaxis, and rapid cycling.

Remission rates in patients with anxiety disorders treated with paroxetine.

BACKGROUND: Approximately 50% to 60% of patients with depression and/or anxiety respond to treatment, but only a minority achieve remission. The continued presence of subsyndromal symptoms in treated depressed (and probably anxious) patients leads to higher relapse rates and increased utilization of health care resources. It is proposed that remission is the appropriate target in the treatment of both depression and the anxiety disorders. AIMS: Rigorous criteria for remission have been proposed for the anxiety disorders and are currently being applied in clinical studies. Using these criteria, data from the paroxetine clinical study database were retrospectively analyzed to determine remission rates following paroxetine treatment across a range of anxiety disorders in the largest analysis of remission data in the anxiety disorders to date. METHOD: These analyses included data from 16 short-term and 6 long-term, randomized, placebo-controlled studies in panic disorder, social anxiety disorder, obsessive-compulsive disorder, posttraumatic stress disorder (short term only), and generalized anxiety disorder (DSM-III-R or DSM-IV). Separate analyses were performed for each disorder, with short- and long-term data analyzed separately. RESULTS: In general, across the range of anxiety disorders studied, in both short- and long-term studies, remission rates were higher for paroxetine compared with placebo, using disorder-specific, global, and functional remission criteria both individually and combined. Remission occurred in a moderate proportion of paroxetine-treated patients after only 8 to 12 weeks of treatment, and longer-term therapy led to even higher remission rates. CONCLUSION: Paroxetine has demonstrated efficacy in treating patients to remission across the range of anxiety disorders studied. Our findings strongly suggest that continuing treatment with paroxetine (and probably other SSRI antidepressants) for 2 to 12 months increases the proportion of patients achieving clinical remission.

Consensus statement update on posttraumatic stress disorder from the international consensus group on depression and anxiety.

OBJECTIVE: To provide an update to the "Consensus Statement on Posttraumatic Stress Disorder From the International Consensus Group on Depression and Anxiety" that was published in a supplement to The Journal of Clinical Psychiatry (2000) by presenting important developments in the field, the latest recommendations for patient care, and suggestions for future research. PARTICIPANTS: The 4 members of the International Consensus Group on Depression and Anxiety were James C. Ballenger (chair), Jonathan R. T. Davidson, Yves Lecrubier, and David J. Nutt. Other faculty who were invited by the chair were Randall D. Marshall, Charles B. Nemeroff, Arieh Y. Shalev, and Rachel Yehuda. EVIDENCE: The consensus statement is based on the 7 review articles in this supplement and the related scientific literature. CONSENSUS PROCESS: Group meetings were held over a 2-day period. On day 1, the group discussed topics to be represented by the 7 review articles in this supplement, and the chair identified key issues for further debate. On day 2, the group discussed these issues to arrive at a consensus view. After the group meetings, the consensus statement was drafted by the chair and approved by all faculty. CONCLUSION: There have been advancements in the science and treatment of posttraumatic stress disorder. Attention to this disorder has increased with recent world events; however, continued efforts are needed to improve diagnosis, treatment, and prevention of posttraumatic stress disorder.

Neural correlates of speech anticipatory anxiety in generalized social phobia.

Patients with generalized social phobia fear embarrassment in most social situations. Little is known about its functional neuroanatomy. We studied BOLD-fMRI brain activity while generalized social phobics and healthy controls anticipated making public speeches. With anticipation minus rest, 8 phobics compared to 6 controls showed greater subcortical, limbic, and lateral paralimbic activity (pons, striatum, amygdala/uncus/anterior parahippocampus, insula, temporal pole)--regions important in automatic emotional processing--and less cortical activity (dorsal anterior cingulate/prefrontal cortex)--regions important in cognitive processing. Phobics may become so anxious, they cannot think clearly or vice versa.

Anxiety and Depression: Optimizing Treatments.

Properly diagnosing and treating patients with anxiety, depression, or both is a challenging aspect of practicing medicine in the primary care setting. Patients often present with somatic complaints rather than classic psychiatric symptoms. In addition, there is significant overlap between anxiety and depression in this patient population. Comorbid anxiety and depression is often more resistant to pharmacologic treatment, and patients with coexisting disorders have a poorer medical prognosis than do patients with either disorder alone. Fortunately, many new therapies are available to assist the clinician in managing these patients. The newer antidepressants, in particular, are playing an increasingly important role in the treatment of both anxiety disorders alone and comorbid anxiety and depression. These new choices enable our goal of treatment to encompass not only improvement but also sustained complete remission. Of the newer agents, the selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors have been studied quite extensively in these patient populations. The specific profiles of individual agents may assist the clinician in individualizing treatment. Characteristics such as robust efficacy, speed of onset of activity, the potential for drug-drug interactions, dose response, and tolerability are important considerations in optimizing treatment.

A Proposed Algorithm for Improved Recognition and Treatment of the Depression/Anxiety Spectrum in Primary Care.

The International Consensus Group on Depression and Anxiety has held 7 meetings over the last 3 years that focused on depression and specific anxiety disorders. During the course of the meeting series, a number of common themes have developed. At the last meeting of the Consensus Group, we reviewed these areas of commonality across the spectrum of depression and anxiety disorders. With the aim of improving the recognition and management of depression and anxiety in the primary care setting, we developed an algorithm that is presented in this article. We attempted to balance currently available scientific knowledge about the treatment of these disorders and to reformat it to provide an acceptable algorithm that meets the practical aspects of recognizing and treating these disorders in primary care.

A pilot study of vagus nerve stimulation (VNS) for treatment-resistant anxiety disorders.

BACKGROUND: Vagus nerve stimulation (VNS) is an effective anticonvulsant device and has shown antidepressant effects in chronic treatment resistant depression. Because the vagus nerve sends information to brain regions important in anxiety regulation (locus coeruleus, orbitofrontal cortex, insula, hippocampus and amygdala), this pathway might be involved in perceiving or manifesting various somatic and cognitive symptoms that characterize anxiety disorders. On the basis of this reasoning and reports of anxiolytic effects of VNS in patients treated for epilepsy and depression, we organized an open-label pilot acute trial of adjunctive VNS on top of stable medications, followed by long-term follow-up, to assess the safety and potential efficacy of VNS for patients with treatment resistant anxiety disorders. METHODS: Eleven adult outpatients with treatment resistant obsessive-compulsive disorder (OCD), panic disorder (PD), or posttraumatic stress disorder (PTSD) were recruited. Patients had failed several medication trials as well as cognitive behavioral therapy (CBT). All patients were rated with the Hamilton Anxiety Scale (HAM-A) and the clinical global impressions improvement scale (CGI-I). Patients with OCD were also rated with the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). Patients were maintained on their current psychotropic medications at fixed doses during the acute 12-week phase. Changes in medications and VNS stimulus parameters were allowed during the long-term follow-up. Response was defined as a 50% or greater improvement on the HAM-A for all patients and a 25% or greater improvement on the Y-BOCS for patients with OCD. RESULTS: Eleven patients were recruited. Seven patients had a primary diagnosis of OCD, two had PTSD, and one had PD. One OCD patient changed their mind and was never implanted. One patient with OCD withdrew consent before the end of the acute phase, so long-term results were available for nine patients. Three patients were acute responders, based on the HAM-A, and there was some improvement in anxiety ratings over time (with statistically significant improvements at 14 of 18 quarters during long-term follow-up). Of the seven patients with OCD who received stimulation, three were acute responders, based on the Y-BOCS, and there was some improvement in Y-BOCS scores over time (with statistically significant improvements at 7 of 18 quarters during long-term follow-up). VNS was relatively well tolerated. Four years after implantation, four patients (diagnoses two OCD, one PD, one PTSD) were still receiving VNS with continued and sustained improvement in anxiety scores compared with their baseline scores. CONCLUSIONS: These patients with treatment-resistant anxiety disorders generally tolerated VNS treatment, and there was evidence of acute and long-term improvement in some patients. These open data suggest that further double-blind studies assessing the VNS role in treating anxiety disorders, particularly OCD, may be warranted.

Generalized anxiety disorder: comorbidity, comparative biology and treatment.

Generalized anxiety disorder (GAD) is a severe and chronic anxiety disorder characterized by uncontrollable worrying and somatic anxiety (tension, insomnia and hypervigilance). It is a common condition, with lifetime prevalence rates for DSM-IV GAD in the general population of approx. 5-6% being reported. In addition, like other anxiety disorders, GAD also shows comorbidity with depression and most of the other anxiety disorders. This article reviews data on the prevalence of GAD, its comorbidity with depression, and its social and economic impact. Proposed neurobiological mechanisms for GAD are discussed, since an understanding of these may help in the development of future therapies. Finally, current pharmacological and non-pharmacological treatment options for GAD are reviewed, with particular attention being paid to published clinical-trial data.