The presentations and clinical courses of patients with bipolar disorder differ greatly by gender. In addition, medical therapy must be tailored differently for men and women because of emerging safety concerns unique to the female reproductive system. In November 2005, these topics were explored by a panel of experts in psychiatry, neurology, and reproductive health at a closed roundtable meeting in Dallas, Texas. This clinical information monograph summarizes the highlights of that meeting.

Compared to men with bipolar disorder, women have more pervasive depressive symptoms and experience more major depressive episodes. They are also at higher risk for obesity and certain other medical and psychiatric comorbidities. Mood changes across the menstrual cycle are common, although the severity, timing, and type of changes are variable. Bipolar disorder is frequently associated with menstrual abnormalities and ovarian dysfunction, including polycystic ovarian syndrome. Although some cases of menstrual disturbance precede the treatment of bipolar disorder, it is possible that valproate and/or antipsychotic treatment may play a contributory role in young women.

Pregnancy does not protect against mood episodes in untreated women. Maintenance of euthymia during pregnancy is critical because relapse during this period strongly predicts a difficult postpartum course. Suspending therapy in the first months of pregnancy may be an option for some women with mild-to-moderate illness, or those with a long history of euthymia during pre-pregnancy treatment. However, a mood stabilizer should be reintroduced either in the later stages of pregnancy or in the immediate postpartum period. Preliminary data suggest that fetal exposure to some mood stabilizers may raise the risk of major congenital malformations and neurodevelopmental delays. For women planning to become pregnant, clinicians may consider switching to other drugs before conception. The value and drawbacks of breastfeeding during treatment must be considered in partnership with the patient, with close monitoring of nursing infants thereafter. The risks and benefits of medical treatment for women with bipolar disorder should be carefully reconsidered at each stage of their reproductive lives, with a flexible approach that is responsive to the changing needs of patients and their families.

In the last 20 years, research on substance addictions has changed its focus from the social foundations to the neurobiological foundations. Hence, some behaviors have begun to be considered as equivalent to addiction based on proposed criteria: salience, withdrawal symptoms, tolerance, conflicts, relapse, and mood modifications.

New knowledge about the brain's reward system suggests that “as far as the brain is concerned a reward is a reward, regardless of whether it comes from a chemical stimulus or an experience.”

Pathological gambling was the prototypical addiction disorder, sharing some hallmarks with substance addictions: a high rate of comorbidity and treatment response to pharmacotherapies, such as opioid antagonist. However, compulsive sexual behavior, compulsive exercise, food starving, binge eating, and, most recently, Internet addiction have been gradually conceptualized as non-substance addictions with overlapping features with substance dependence. Several definitions” have been adopted regarding these behaviors: natural addiction, non-chemical addiction, and negative dependence are only some examples. This issue of CNS Spectrums focuses on behavioral addictions.

Anxiety disorders in the United States are prevalent, widespread, and disabling. These illnesses may account for almost one third of the $148 billion total mental health bill each year. Pharmacologic options include tricyclic antidepressants, monoamine oxidase inhibitors, serotonin norepinephrine reuptake inhibitors, selective serotonin reuptake inhibitors, and anxiolytics. Psychological treatments include cognitive-behavioral therapy (CBT), cognitive therapy, exposure, and ritual prevention therapies. Despite insufficient evidence, many experts recommend combined treatment, generally medication with CBT. A literature review was conducted to examine studies with random assignment, adequate methods and sample sizes, blind assessments, sufficient dosages and durations of treatment, and satisfactory reporting of data, to determine whether combined treatment was superior to monotherapy. Twenty-six randomized clinical trials were identified; nine met review criteria. A review of relevant studies could not confirm the superiority of combined treatment over monotherapy. In one of four studies of obsessive-compulsive disorder, combined treatment produced better results than monotherapy.  There was no evidence of superiority for combined therapy over monotherapy for the treatment of social phobia or generalized anxiety disorder. There were no studies that met review criteria for either specific phobia or posttraumatic stress disorder (PTSD). With panic disorder, there was evidence that combined treatment might actually lead to worse outcome. Combined treatment is commonly recommended, but empirical support is limited. More research is needed. There are few well-designed studies, and little data regarding PTSD and specific phobias.

This article reviews the theory, clinical application, and empirical findings on mindfulness–based cognitive therapy (MBCT) for mental health and addictive disorders. Expanding upon the research demonstrating the efficacy of cognitive-behavioral therapy (CBT) for addiction, this article develops and explores the rationale for combining mindfulness-based interventions with evidence-based CBTs in treating addictive disorders, with an emphasis on substance use disorders with co-occurring mood disorders.This article proposes that deficits in affect regulation — related to the behavioral and emotional effects of neurobiological changes that occur with longterm substance abuse — pose a unique set of challenges in early recovery. Prolonged use of addictive substances impairs the brain pathways to detach or maintain perspective in response to strong emotional states. In treating this affective dysregulation, which can contribute to the vulnerability to relapse in the early stages of recovery, the affect–regulation-specific focus of MBCT adds a valuable element to augment CBT for addiction. Summarizing magnetic resonance imaging and positron emission tomography findings on the effects of MBCT and the neurobiology of drug addiction, this article out-lines directions for further research on potential benefits of MBCT for the recovering individual. Finally, this article describes a structured protocol, developed at the Mount Sinai School of Medicine in New York City, which combines CBT with mindfulness-based intervention, for the treatment of affect-regulation issues specific to co-occurring addictive and mood disorders.

Cutaneous rashes and eruptions can be caused by many medications, including carbamazepine. The presentation can be varied depending on severity. Cutaneous eruptions occur in 3% of individuals administered carbamazepine. Angioedema, a rare side effect of carbamazepine, involves vascular leakage in dermis and subcutis mediated by immunoglobulin E and/or bradykinins. Angioedema is more common in females and in the third decade of life. We report the case of a 27-year-old Indian woman who developed maculopapular rash and angioedema secondary to carbamazepine administration. The patient responded successfully to withdrawal of the drug and treatment with antihistamines. Due to the potentially life-threatening complications of this condition and the increasing use of anticonvulsants in the treatment of mood disorders, psychiatrists must be aware of the diagnosis and treatment of this condition.

Objective: To describe a case of marijuanainduced delirium and the techniques used to detect psychoactive agents and metabolites in urine.

Methods: A case of delirium following involuntary ingestion of cannabis is described. A urine sample was analyzed applying various chemical procedures, using high-resolution gas chromatography coupled with mass spectrometry technique. 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid was quantified by the methodology for steroids and cannabis.

Results: A 26-year-old man was hospitalized with severe agitation and psychotic behavior 36 hours after suspected involuntary ingestion of cannabis contained in a brigadeiro, a typical Brazilian cookie, consumed during a party. Treatment with neuroleptics resulted in complete regression of the symptoms over 2 weeks. The urine sample revealed marijuana ingestion, demonstrated by the presence of its metabolite, 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid in

Conclusion: Severe delirium can follow oral ingestion of cannabis integrated into homemade cookies.

The presentations and clinical courses of patients with bipolar disorder differ greatly by gender. In addition, medical therapy must be tailored differently for men and women because of emerging safety concerns unique to the female reproductive system. In November 2005, these topics were explored by a panel of experts in psychiatry, neurology, and reproductive health at a closed roundtable meeting in Dallas, Texas. This clinical information monograph summarizes the highlights of that meeting.

Compared to men with bipolar disorder, women have more pervasive depressive symptoms and experience more major depressive episodes. They are also at higher risk for obesity and certain other medical and psychiatric comorbidities. Mood changes across the menstrual cycle are common, although the severity, timing, and type of changes are variable. Bipolar disorder is frequently associated with menstrual abnormalities and ovarian dysfunction, including polycystic ovarian syndrome. Although some cases of menstrual disturbance precede the treatment of bipolar disorder, it is possible that valproate and/or antipsychotic treatment may play a contributory role in young women.

Pregnancy does not protect against mood episodes in untreated women. Maintenance of euthymia during pregnancy is critical because relapse during this period strongly predicts a difficult postpartum course. Suspending therapy in the first months of pregnancy may be an option for some women with mild-to-moderate illness, or those with a long history of euthymia during pre-pregnancy treatment. However, a mood stabilizer should be reintroduced either in the later stages of pregnancy or in the immediate postpartum period. Preliminary data suggest that fetal exposure to some mood stabilizers may raise the risk of major congenital malformations and neurodevelopmental delays. For women planning to become pregnant, clinicians may consider switching to other drugs before conception. The value and drawbacks of breastfeeding during treatment must be considered in partnership with the patient, with close monitoring of nursing infants thereafter. The risks and benefits of medical treatment for women with bipolar disorder should be carefully reconsidered at each stage of their reproductive lives, with a flexible approach that is responsive to the changing needs of patients and their families.

Posttraumatic stress disorder (PTSD) has a discernible starting point and typical course, hence the particular appropriateness of longitudinal research in this disorder. This review outlines the salient findings of longitudinal studies published between 1988 and 2004. Studies have evaluated risk factors and risk indicators of PTSD, the disorder's trajectory, comorbid disorders and the predictive role of acute stress disorder. More recent studies used advanced data analytic methods to explore the sequence of causation that leads to chronic PTSD. Advantages and limitations of longitudinal methods are discussed.

Scientific literature has never described a poor metabolizer for both the cytochrome P450 (CYP) 2D6 and the CYP 2C19. They are expected to be rare (<1% in different ethnic groups) and prone to adverse drug reactions with many antidepressants. In an ongoing pharmacogenetic study, after genotyping 1,576 subjects in three Kentucky state hospitals we have found one poor metabolizer for both CYP 2D6 and CYP 2C19, which corresponds to a prevalence of 0.06% (95% Cl 0.01 to 0.36).The naturalistic antidepressant treatment of this poor metabolizer for both enzymes is described in this article. As genotyping reaches clinical practice, it will be interesting to prospectively establish whether mirtazapine is a reasonable choice as an antidepressant for these patients, as the data and this case suggest.

Recurrent major depressive disorder (MDD) is a common and disabling illness, but few studies have addressed long-term antidepressant treatment of recurrent MDD (ie, beyond 1 year of maintenance therapy) or compared the efficacy and safety of different antidepressant classes in this population. This article describes the rationale and design of a unique multi-phase trial in patients with recurrent MDD. The Prevention of Recurrent Episodes of Depression with Venlafaxine for Two Years (PREVENT) study is a large double-blind, randomized, multi-center trial designed to assess the long-term efficacy of venlafaxine extended release (ER) in the prevention of depressive recurrence. Approximately 1,100 adult outpatients with MDD and a history of ≥3 lifetime episodes (with at least two occurring in the past 5 years) were randomized to 10 weeks of acute-phase treatment with either venlafaxine ER 75–300 mg/day or fluoxetine 20–60 mg/day, followed by 6 months of continuation-phase treatment for patients experiencing a satisfactory therapeutic response or remission during the acute phase. Responders and remitters to continuation phase treatment were then entered into a 2-year maintenance phase study, in which those receiving venlafaxine ER were re-randomized to either venlafaxine ER or placebo at the start of two 12-month maintenance periods. Those taking fluoxetine during the acute and continuation phases continued to receive double-blind treatment with fluoxetine. This study will address several unanswered questions about the long-term treatment of recurrent MDD, such as whether extended maintenance treatment (ie, up to 2 years) lessens the risk for developing future depressive episodes; whether fluoxetine and venlafaxine ER are effective for both short- and long-term treatment of MDD; whether rates of tachyphylaxis differ between anti- depressant classes; and whether the likelihood of depressive recurrence differs according to the time point when treatment is discontinued.

Somatization disorder, multiple chemical sensitivities, chronic fatigue syndrome, fibromyalgia, Gulf War syndrome, neurasthenia, irritable bowel syndrome, conversion disorder…idiopathies one and all. These syndromes and the many others like them have perhaps one overriding commonality: enormous unexplained heterogeneity. Patients and clinicians gaze into the suffering and impact of these symptoms and see as many potential causes as there are symptom combinations.

Whose explanation is best? When I am speaking with psychiatrists, the notion of somatoform symptoms goes largely unchallenged. When I am with rheumatologists, however, fibromyalgia is anything but a psychiatric problem and certainly not a somatoform disorder. Among my toxicologist colleagues, it is readily accepted that low-tevel toxic exposures could account for many idiopathic “sensitivities.”

But what of the high rate of depression and anxiety disorders we see in these patients?” I sometimes unwisely retort.

“Well, it could be a co-factor or an interaction,” is a common response.

Unshaken, I step further into the abyss: “How, then, do you explain the high rate of adverse childhood experiences among people with idiopathic symptom syndromes?”

The response is swift. “You cannot rule out biased recall. We cannot expect people to remember these things accurately in such a negative state of mind.”

And so it goes. After several of these kinds of conversations, I have finally concluded there is no point in arguing.The debate is largely irreconcilable, a debate that strikingly parallels the conflicts many primary care physicians experience with symptomatic patients. “How is your personal life?” the doctor may ask a symptomatic patient, suspecting a psychosocial explanation.

The overall effectiveness of antipsychotics for the management of schizophrenia is restricted by their side-effect profiles, particularly over an extended treatment period. Intolerable side effects can reduce patient adherence to medication and often lead to treatment discontinuation. Some side effects that result from antipsychotic use are precursors to the metabolic syndrome, which is prevalent among individuals with schizophrenia and represents a significant source of cardiovascular risk. The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia study assessed the efficacy of the atypical antipsychotics olanzapine, quetiapine, risperidone, and ziprasidone relative to the conventional drug perphenazine. Additional assessments included the metabolic effects of these agents in patients with schizophrenia and the incidence of negative side effects. No significant differences were found between treatment groups for time to discontinuation due to intolerability, but the rates of side effects significantly differed (P=.04). For metabolic parameters, olanzapine was associated with greater and significant adverse effects on weight, lipids, and glucose metabolism versus the other antipsychotics tested. The CATIE results show that important distinctions exist among currently available atypical antipsychotics. Physicians should be aware of the propensity of these drugs to increase the risks of cardiovascular disease and diabetes in treated patients and tailor individual treatment decisions accordingly. This article highlights the metabolic findings from the CATIE schizophrenia study, and explores the differences shown by atypical antipsychotics, with regard to metabolic side effects that increase cardiovascular risk.

Psychotropic drugs are often associated with sexual dysfunction. The frequency of antidepressant-associated sexual dysfunction is greatly underestimated in clinical trials that rely on patient self-report of these adverse events. Direct inquiry reveals that delayed orgasm/ejaculation occurs in ≥50% and anorgasmia in at least one third of patients given selective serotonin reuptake inhibitors. Antidepressant-induced sexual dysfunction can be successfully managed. A different antidepressant without significant sexual effects, such as bupropion or mirtazapine, can often be substituted. Other strategies involve drug holidays or adjunctive therapy with drugs such as sildenafil. Dopamine antagonist antipsychotic drugs are most commonly associated with decreased libido. The newer atypical antipsychotics, with less effect on dopamine, are less commonly associated with sexual dysfunction. Sexual dysfunction is commonly reported with seizure disorders, and many anticonvulsant drugs affect levels of sex hormones. Because sexual dysfunction can be related to many factors, care must be taken to establish the patient's baseline sexual functioning before the initiation of psychotropic drug therapy and to rule out other etiologies before drugs are implicated as causative.