Understanding the role of adjunctive nonpharmacological therapies in management of the multiple pathways to depression.

Major depressive disorder (MDD) is a common disorder with a lifetime prevalence of 16.2% and the fourth highest cause of disability globally. It is hypothesized to be a syndromatic manifestation of multiple pathological processes leading to similar clinical manifestation. MDD is associated with at least three categories of peripheral hormone-type factors including neurotrophic factors, proinflammatory cytokines, and processes that impair regulation of the hypothalamic-pituitary-adrenocortical axis. Neuroimaging studies have identified functional abnormalities including subcortical systems associated with reward and emotion processing, medial prefrontal and anterior cingulate cortical regions and the lateral prefrontal cortical systems involved in cognitive control and voluntary emotion regulation. Studies investigating the effects of psychotherapy and pharmacotherapy on functional brain measures show normalization of brain function with return to euthymia. Nevertheless, approximately 50% of patients with MDD will not respond sufficiently and 60 to 70% will not achieve full remission with first-line pharmacotherapy, therefore clinicians strive to improve patient responses through the use of adjunct therapies. This review discusses recent research in the various biological processes associated with MDD as well as recent data in support of the use of adjunctive non-pharmacological therapies including psychotherapy, bibliotherapy, Internet therapy, "natural" or herbal approaches, exercise therapy, and somatic therapies.

Efficacy of acupuncture treatment of sexual dysfunction secondary to antidepressants.

BACKGROUND: Antidepressants including selective serotonin reuptake inhibitors (SSRIs) and serotonin noradrenaline reuptake inhibitors (SNRIs) are known to cause secondary sexual dysfunction with prevalence rates as high as 50%-90%. Emerging research is establishing that acupuncture may be an effective treatment modality for sexual dysfunction including impotence, loss of libido, and an inability to orgasm. OBJECTIVES: The purpose of this study was to examine the potential benefits of acupuncture in the management of sexual dysfunction secondary to SSRIs and SNRIs. SUBJECTS: Practitioners at the START Clinic referred participants experiencing adverse sexual events from their antidepressant medication for acupuncture treatment at the Mood and Anxiety Disorders, a tertiary care mood and anxiety disorder clinic in Toronto. DESIGN: Participants received a Traditional Chinese Medicine assessment and followed an acupuncture protocol for 12 consecutive weeks. The acupuncture points used were Kidney 3, Governing Vessel 4, Urinary Bladder 23, with Heart 7 and Pericardium 6. Participants also completed a questionnaire package on a weekly basis. OUTCOMES MEASURED: The questionnaire package consisted of self-report measures assessing symptoms of depression, anxiety, and various aspects of sexual function. RESULTS: Significant improvement among male participants was noted in all areas of sexual functioning, as well as in both anxiety and depressive symptoms. Female participants reported a significant improvement in libido and lubrication and a nonsignificant trend toward improvement in several other areas of function. CONCLUSIONS: This study suggests a potential role for acupuncture in the treatment of the sexual side-effects of SSRIs and SNRIs as well for a potential benefit of integrating medical and complementary and alternative practitioners.

A multicomponent yoga-based, breath intervention program as an adjunctive treatment in patients suffering from generalized anxiety disorder with or without comorbidities.

OBJECTIVES: The aim of this study is to evaluate the efficacy and tolerability of Sudarshan Kriya Yoga (SKY) course in generalized anxiety disorder (GAD) outpatients, who after eight weeks of an appropriate dose of traditional therapy had not yet achieved remission. SUBJECTS: The adult participants (18-65 years) were outpatients with a primary diagnosis of GAD with or without comorbidities on the Mini-International Neuropsychiatric Interview (MINI). Participants had a minimum of eight weeks standard treatment with an appropriate dose of a standard prescription anxiolytic, a clinician global impression-severity (CGI-S) score of 5-7, a Hamilton anxiety scale (HAM-A) total score ≥20 including a score of >2 on the anxious mood and tension items. MATERIALS AND METHODS: Forty-one patients were enrolled in an open-label trial of the SKY course as an adjunct to standard treatment of GAD at the START Clinic for Mood and Anxiety Disorders, a tertiary care mood and anxiety disorder clinic in Toronto. The SKY course was administered over five days (22 h total). Subjects were encouraged to practice the yoga breathing techniques at home for 20 min per day after the course and were offered group practice sessions for 2 h once a week led by certified yoga instructors. The primary outcome measure was the mean change from pre-treatment on the HAM-A scale. Psychological measures were obtained at baseline and four weeks after completing the intervention. RESULTS: Thirty-one patients completed the program (mean age 42.6 ± 13.3 years). Among completers, significant reductions occurred in the pre- and post-intervention mean HAM-A total score (t=4.59; P<0.01) and psychic subscale (t=5.00; P≤0.01). The response rate was 73% and the remission rate 41% as measured on the HAM-A. CONCLUSION: The results of this small pilot trial suggest that the SKY course represents a potentially valuable adjunct to standard pharmacotherapy in patients with GAD or treatment-resistant GAD, and warrants further investigation. In particular, changes in worry and body symptoms showed significant improvements that may further our understanding of the mechanism of change in the tolerance of anxiety and worry.

Rates of detection of mood and anxiety disorders in primary care: a descriptive, cross-sectional study.

OBJECTIVE: To determine the incidence of major depressive disorder, bipolar disorder, panic disorder, social anxiety disorder, and generalized anxiety disorder and to assess their detection rates in the Canadian primary care setting. METHOD: The descriptive, cross-sectional study was conducted in 7 primary care clinics in 3 Canadian provinces, Ontario, British Columbia, and Nova Scotia, from December 6, 2005, to May 5, 2006. Patients in clinic waiting rooms who consented to participate in the study were administered the Mini International Neuropsychiatric Interview (MINI) (N = 840). These patients' medical charts were then reviewed for evidence of previous diagnosis of a mood or anxiety disorder. Misdiagnosis was defined as cases for which a diagnosis was reached on the MINI but not in the patient's chart. RESULTS: Of the 840 primary care patients assessed, 27.2%, 11.4%, 12.6%, 31.2%, and 16.5% of patients met criteria for major depressive disorder, bipolar disorder, panic disorder, generalized anxiety disorder, and social anxiety disorder, respectively. Misdiagnosis rates reached 65.9% for major depressive disorder, 92.7% for bipolar disorder, 85.8% for panic disorder, 71.0% for generalized anxiety disorder, and 97.8% for social anxiety disorder. CONCLUSIONS: With high prevalence rates and poor detection, there is an obvious need to enhance diagnostic screening in the primary care setting.

What makes people anxious about pain? How personality and perception combine to determine pain anxiety responses in clinical and non-clinical populations.

Although anxiety has both dispositional and situational determinants, little is known about how individuals' anxiety-related sensitivities and their expectations about stressful events actually combine to determine anxiety. This research used Information Integration Theory and Functional Measurement to assess how participants' physical concerns sensitivity (PCS) and event expectancy are cognitively integrated to determine their anxiety about physical pain. Two studies were conducted - one with university students and other with anxiety clinic patients - in which participants were presented with multiple scenarios of a physically painful event, each representing a different degree of event probability from which subjective expectancies were derived. Independent variables included PCS (low, moderate, and high) and event expectancy (low-, medium-, high-, and non-probability information). Participants were asked to indicate their projected anxiety (dependent measure) in each expectancy condition in this 3 × 4 mixed, quasi-experimental design. The results of both studies strongly suggest that PCS and event expectancy are integrated additively to produce these pain anxiety scores. Additional results and their implications for the treatment of anxiety-related disorders are also discussed.

Weight gain and psychiatric treatment: Is there a role for green tea and conjugated linoleic acid?

Dietary supplement use is widespread in developed nations. In particular, patients who utilize mental health services also report frequent consumption of dietary supplements, often in relation to management of adverse events and specifically weight gain. Weight gain induced by psychotropic medications can further compound psychological distress and negatively influence compliance. Here we report on four cases of social anxiety disorder treated with the atypical antipsychotic quetiapine. Self-administration of conjugated linoleic acid and green tea extract may have influenced objective anthropomorphic measurements; each patient had an unexpected decrease in total body fat mass, a decrease in body fat percentage and an increase in lean body mass. Since weight gain is a common and undesirable side-effect with psychiatric medications, our observation strongly suggests the need for controlled clinical trials using these agents.

Pharmacotherapy of post-traumatic stress disorder: a family practitioners guide to management of the disease.

Post-traumatic stress disorder is a difficult to treat, yet common disorder, which is associated with significant morbidity, mortality and societal burden. Comprehensive management of post-traumatic stress disorder must include both psychotherapeutic and pharmacologic components. The current evidence-based pharmacologic management approaches to post-traumatic stress disorder, suggests that first-line treatments for monotherapy are the selective serotonin reuptake inhibitors, sertraline, paroxetine and fluoxetine. Other potential options include other monotherapies including venlafaxine, mirtazapine, tricyclic antidepressants, monoamine oxidase inhibitors, as well as adjunctive usage of atypical antipsychotics, lamotrigine, trazadone and a number of adrenergic agents. A trial of therapy should be at least 8 weeks and continue for at the very least 12 months, but is likely to be much longer. In light of the risks of untreated post-traumatic stress disorder (e.g., suicide and impaired psychosocial functioning), therapy may need to be continued for 2 years or more. Pharmacologic therapy instituted at the time of acute psychologic trauma shows promise for the prevention of post-traumatic stress disorder in the future and warrants further study.

Treatments for generalized anxiety disorder.

Generalized anxiety disorder is characterized by excessive chronic anxiety in association with many somatic symptoms. The disorder has pervasive effects on quality of life, including work, social and educational aspects and requires long-term therapy. Available studies in patients are the Diagnostic and Statistical Manual of Mental Disorders, third edition-revised and fourth edition, which have defined generalized anxiety disorder and demonstrate the efficacy of benzodiazepines, azapirones, some antidepressants and psychotherapy. Benzodiazepines are effective anxiolytics for short-term use but are accompanied by many adverse events. The antidepressants, paroxetine and venlafaxine (Efexor), have demonstrated efficacy in patients with generalized anxiety disorder with mild side-effect profiles. They have the additional benefit of efficacy in depression, which frequently occurs comorbidly in these patients. Long-term efficacy has been shown with venlafaxine in the treatment of this chronic condition, confirming that as in depression, the goal must not just be remission beyond simple symptom resolution but also on to improved functioning and quality of life. Psychotherapy with applied relaxation, cognitive therapy and cognitive behavioral therapy show the most promise in resolving and maintaining treatment gains in the long-term. These approaches may be useful alone or in combination with adjunctive pharmacotherapy to achieve remission. Based on current evidence, the recommended approach to achieving long-term benefits for patients with generalized anxiety disorder is antidepressant therapy with paroxetine or venlafaxine in combination with cognitive behavioral therapy.

Anxiety sensitivity as a predictor of panic attacks.

Anxiety sensitivity (AS) is the fear of physical symptoms of anxiety and related sensations believed to have harmful consequences. AS may play a central role in the nature and etiology of panic disorder (PD) and the genesis of panic attacks. We collected Anxiety Sensitivity Index (ASI) scores from PD patients and controls to determine if AS accurately predicts panic. ASIs were completed prior to panic induction using the modified Read rebreathing test in both hypoxic and hyperoxic conditions. Total scores first-order factors, and individual item ASI scores were correlated with panic presence (Spearman correlation) for each of the hypoxic and hyperoxic rebreathing tests for both study populations. Control subjects' data correlated significantly for items 4, 8, and 11 of the ASI for the hyperoxic (n=9; r(S)=0.63, 0.70, and 0.63, respectively) and items 4 and 8 for the hypoxic rebreathing tests (n = 9; r(S) = 0.63 and 0.70, respectively). Panic patients' data correlated significantly for item 1 of the ASI for hyperoxic tests (n=8; r(S)=0.76) and item 5 for the hypoxic tests (n = 8; r(S) = 0.95). Total ASI scores or first-order factors (physical, social concerns, and mental incapacitation) scores of either study group did not correlate significantly with panic presence. AS may not be a reliable predictor of panicogenic responses to CO2-induced panic in either PD or normal control populations. AS may not be an ultimate causal element in eliciting panic attacks.

Methyl nicotinate-induced vasodilation in generalized social phobia.

Elevated vasodilatory response (blushing) to social situations is characteristic of social phobia (SP). A relatively unexplored basis for this phenomenon is alteration in underlying vasodilatory mechanisms. To investigate this possibility, we evaluated the vasodilatory response induced by methyl nicotinate (niacin ester derivative) in 31 generalized SP patients and 41 matched healthy volunteers (HV). A patch impregnated with 0, 0.1, 0.5, 1, and 10 mM methyl nicotinate was applied to the forearm or face of subjects for 1 min, followed by 20-min laser Doppler spectroscopy blood flow monitoring. Blood flow stimulation with 1 and 10 mM methyl nicotinate was significantly reduced in SP patients by 35 and 17%, respectively. Induced blood flow was negatively correlated with patients' Leibowitz Social Phobia Scale (LSAS) at 1 and 10 mM doses. Furthermore, the maximal rate of change of vasodilatory reaction was correlated with symptom scores at 1 and 10 mM doses. Induced increases in the arm and face blood flow measurements correlated, supporting the external validity of the former location. Generalized SP patients vasodilate less to topical methyl nicotinate challenges, with effect amplification in severely ill patients. Although the mechanism for this is unclear, we propose desensitization of the prostaglandin-mediated vasodilating system as an explanation. Neuropsychopharmacology (2003) 28, 1846-1851, advance online publication, 23 July 2003; doi:10.1038/sj.npp.1300227

Effects of tryptophan depletion on central and peripheral chemoreflexes in man.

Klein (Arch. Gen. Psychiatry 50, 306-317, 1993) suggests that panic attacks are the result of a defective 'suffocation alarm' threshold that presents with carbon dioxide (CO(2)) hypersensitivity, exaggerated ventilatory response and panic in panic disorder (PD) patients. Serotonergic deficiencies enhance this ventilatory response in PD patients, as per 'suffocation alarm' theory predictions, suggesting that serotonin (5-HT) normalizes the ventilatory response. Other research supports a serotonin system-mediated stimulation of ventilation. Knowledge of 5-HT's role on ventilatory output and its neurophysiological sources impacts on the 'suffocation alarm' theory validity and predictive value. We used tryptophan depletion (TRP-) in concert with a modified Read rebreathing test to determine the effect of deficient serotonergic modulation on the central and peripheral chemoreflex threshold and sensitivity of response to CO(2) in 11 healthy men. TRP- did not affect central or peripheral chemoreflex threshold or sensitivity of response to CO(2). However, basal ventilation was significantly elevated during TRP-. In contrast to 'suffocation alarm' theory predictions, decreased 5-HT neurotransmission does not significantly affect the respiratory chemoreflex response to CO(2), impacting on non-chemoreflex drives to breathe. Panic associated respiratory abnormalities may be related to defective 5-HT modulation of non-chemoreflex drives to breathe, unrelated to any respiratory chemoreflex abnormality.