Anxiety Disorders: Stanford University

Hayward C, Sanborn K. · Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California 94305, USA. · J Adolesc Health. · Pubmed #11943575 No free full text.

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Wilhelm FH, Gevirtz R, Roth WT. · Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Laboratory of Clinical Psychopharmacology and Psychophysiology, Stanford University, USA. · Behav Modif. · Pubmed #11530714 No free full text.

Abstract: Respiration is a complex physiological system affecting a variety of physical processes that can act as a critical link between mind and body. This review discusses the evidence for dysregulated breathing playing a role in three clinical syndromes: panic disorder, functional cardiac disorder, and chronic pain. Recent technological advances allowing the ambulatory assessment of endtidal partial pressure of CO2 (PCO2) and respiratory patterns have opened up new avenues for investigation and treatment of these disorders. The latest evidence from laboratories indicates that subtle disturbances of breathing, such as tidal volume instability and sighing, contribute to the chronic hypocapnia often found in panic patients. Hypocapnia is also common in functional cardiac and chronic pain disorders, and studies indicate that it mediates some of their symptomatology. Consistent with the role of respiratory dysregulation in these disorders, initial evidence indicates efficacy of respiration-focused treatment.

Wilhelm FH, Roth WT. · Stanford University, School of Medicine and VAPA Health Care System (116F-PAD), 3801 Miranda Avenue, Palo Alto, CA 94304, USA. · Biol Psychol. · Pubmed #11454436 No free full text.

Abstract: Although DSM-IV criteria for anxiety disorders include physiological symptoms, these symptoms are evaluated exclusively by verbal report. The current review explores the background for this paradox and tries to demonstrate on theoretical and empirical grounds how it could be resolved, providing new insights about the role of psychophysiological measures in the clinic. The three-systems approach to evaluating anxiety argues that somatic measures as well as verbal and behavioral ones are indispensable. However, the low concordance between these domains of measurement impugns their reliability and validity. We argue that concordance can be improved by examining the relationship of variables less global than anxiety and by restriction to specific anxiety disorders. For example, recent evidence from our and other laboratories indicate a prominent role of self-reported and physiologically measured breathing irregularities in panic disorder. Nonetheless, even within a diagnosis, anxiety patients vary radically in which somatic variables are deviant. Thus, in clinical practice, individual profiles of psychological and physiological anxiety responses may be essential to indicate distinct therapeutic approaches and ways of tracking improvement. Laboratory provocations specific to certain anxiety disorders and advances in ambulatory monitoring vastly expand the scope of self-report and physiological measurement and will likely contribute to a refined assessment of anxiety disorders.

Sapolsky RM. · Department of Biological Sciences, Stanford University, California 94305-5020, USA. · Hippocampus. · Pubmed #11345129 No free full text.

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Sapolsky RM. · Departments of Biological Sciences and Neurological Sciences, Stanford University School, Stanford, CA 94305-5020, USA. · Arch Gen Psychiatry. · Pubmed #11015810 No free full text.

Abstract: An extensive literature stretching back decades has shown that prolonged stress or prolonged exposure to glucocorticoids-the adrenal steroids secreted during stress-can have adverse effects on the rodent hippocampus. More recent findings suggest a similar phenomenon in the human hippocampus associated with many neuropsychiatric disorders. This review examines the evidence for hippocampal atrophy in (1) Cushing syndrome, which is characterized by a pathologic oversecretion of glucocorticoids; (2) episodes of repeated and severe major depression, which is often associated with hypersecretion of glucocorticoids; and (3) posttraumatic stress disorder. Key questions that will be examined include whether the hippocampal atrophy arises from the neuropsychiatric disorder, or precedes and predisposes toward it; whether glucocorticoids really are plausible candidates for contributing to the atrophy; and what cellular mechanisms underlie the overall decreases in hippocampal volume. Explicit memory deficits have been demonstrated in Cushing syndrome, depression, and posttraumatic stress disorder; an extensive literature suggests that hippocampal atrophy of the magnitude found in these disorders can give rise to such cognitive deficits.

Koran LM. · Department of Psychiatry, Stanford University Medical Center, California, USA. · Psychiatr Clin North Am. · Pubmed #10986724 No free full text.

Abstract: Available data suggest that OCD has a substantial adverse effect on the HRQL of sufferers and their families. Although no consensus exists as to how to conceptualize or measure HRQL, studies using various concepts and measures will create a greater appreciation of the suffering and impairment entailed in this illness and a greater understanding of the costs, benefits, and limitations of treatment.

Schatzberg AF. · Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Calif 94305-5548, USA. · J Clin Psychiatry. · Pubmed #10926050 No free full text.

Abstract: The second and third generation of antidepressants, i.e., the selective serotonin reuptake inhibitors, nefazodone, venlafaxine, and mirtazapine, are proving to be useful in a variety of seemingly diverse disorders, including most anxiety disorders. In addition to receiving approval from the U.S. Food and Drug Administration (FDA) for major depressive disorder, some of the newer antidepressants have received FDA approval for other disorders, e.g., generalized anxiety disorder (venlafaxine), bulimia nervosa (fluoxetine), obsessive-compulsive disorder (fluvoxamine, paroxetine, sertraline, and fluoxetine), social phobia (paroxetine), panic disorder (sertraline, paroxetine), and posttraumatic stress disorder (sertraline). In controlled studies, these agents have also shown usefulness in premenstrual dysphoric disorder, borderline personality disorder, obesity, smoking cessation, and alcoholism. This article describes the new and potential indications for recently developed antidepressants and the studies that suggested these indications.

Schatzberg AF. · Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Calif 94305-5717, USA. · J Clin Psychiatry. · Pubmed #10910015 No free full text.

Abstract: The past decade has witnessed the advent of selective serotonin reuptake inhibitors (SSRIs) as first-line treatments for major depression. Still, there is considerable debate as to whether these agents are as effective or as potent as the first-generation tricyclic antidepressants (TCAs) or the mixed reuptake inhibitor, venlafaxine, all of which exert considerable effect on norepinephrine (NE) reuptake. Recently, reboxetine, a selective NE reuptake inhibitor (selective NRI), has been introduced in Europe. This drug has only a minimal affinity for muscarinic acetylcholine receptors and therefore causes less dry mouth, constipation, or other such effects than do the TCAs. Reboxetine does not block serotonin reuptake or alpha1 receptors and, thus, does not appear to produce significant nausea, diarrhea, or hypotension. Unlike other antidepressants, reboxetine appears to be nonsedating. Data on acute and long-term clinical efficacy and safety from double-blind, placebo-controlled, and active comparator studies with reboxetine are reviewed. These studies indicate that reboxetine is significantly more effective than placebo and as effective as fluoxetine in reducing depressive symptoms. Improvements in social adjustments were reported to be more favorable with reboxetine than with fluoxetine. Further, data from controlled clinical trials have shown that the side effect profile for reboxetine is relatively benign. The clinical implications of studies on reboxetine are discussed with an eye toward understanding the potential role NE reuptake blockers may play in the treatment of patients with major depression.

Ketter TA, Post RM, Theodore WH. · Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, California 94305-5723, USA. · Neurology. · Pubmed #10496235 No free full text.

Abstract: Antiepileptic drugs (AEDs) have various mechanisms of actions and therefore have diverse anticonvulsant, psychiatric, and adverse effect profiles. Two global categories of AEDs are identified on the basis of their predominant psychotropic profiles. One group has "sedating" effects in association with fatigue, cognitive slowing, and weight gain, as well as possible anxiolytic and antimanic effects. These actions may be related to a predominance of potentiation of gamma-aminobutyric acid (GABA) inhibitory neurotransmission induced by drugs such as barbiturates, benzodiazepines, valproate, gabapentin, tiagabine, and vigabatrin. The other group is associated with predominant attenuation of glutamate excitatory neurotransmission and has "activating" effects, with activation, weight loss, and possibly anxiogenic and antidepressant effects. This group includes agents such as felbamate and lamotrigine. Agents such as topiramate, with both GABAergic and antiglutamatergic actions, may have "mixed" profiles. Mechanisms of actions, activity in animal models of anxiety and depression, and clinical psychotropic effects of AEDs in psychiatric and epilepsy patients are reviewed in relationship to this proposed categorization. These considerations suggest the testable hypothesis that better psychiatric outcomes in seizure disorder patients could be achieved by treating patients with baseline "activated" profiles (insomnia, agitation, anxiety, racing thoughts, weight loss) with "sedating" predominantly GABAergic drugs, and conversely those with baseline "sedated" or anergic profiles (hypersomnia, fatigue, apathy, depression, sluggish cognition, weight gain) with "activating" predominantly antiglutamatergic agents. Systematic clinical investigation of more precise relationships of discrete mechanisms of actions to psychotropic profiles of AEDs is needed to assess the utility of this general proposition and define exceptions to this broad principle.

Schatzberg AF, DeBattista C. · Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, Calif 94305-5548, USA. · J Clin Psychiatry. · Pubmed #10418809 No free full text.

Abstract: Agitation is a troublesome, common symptom in major depression that can be difficult to manage. It is sometimes a side effect of antidepressant treatment and may occasionally represent a mixed bipolar episode. If agitation fails to respond to an antidepressant alone, treatment may be augmented with a benzodiazepine, a neuroleptic, or lithium. Preliminary evidence indicates that divalproex, which has been found useful for bipolar disorder and for agitation associated with Alzheimer's disease, may also be effective for agitated depression. A controlled trial is now underway.

Glick ID, Poyurovsky M, Ivanova O, Koran LM. · Stanford University School of Medicine, Department of Psychiatry, 401 Quarry Rd., Suite 2122, Stanford, CA 94305, USA. · J Clin Psychiatry. · Pubmed #19026264 No free full text.

Abstract: BACKGROUND: Approximately 15% of patients with schizophrenia also meet DSM-IV criteria for obsessive-compulsive disorder (OCD) at some point in their illness, a rate considerably higher than in the general population. This study examined aripiprazole treatment of patients with comorbid schizophrenia and obsessive-compulsive symptoms (OCS) that did not meet full criteria for OCD. METHOD: Physically healthy adults aged 18 to 65 years with DSM-IV schizophrenia and a minimum score of 16 on the Yale-Brown Obsessive Compulsive Scale (YBOCS) were eligible to participate in this 6-week, open-label, flexible-dose trial of aripiprazole monotherapy. Patients currently taking another antipsychotic medication were concurrently down-titrated from their current antipsychotic and up-titrated with aripiprazole, starting with 15 mg/day. Coadministration of the 2 medications lasted from 7 to 14 days, until a stable therapeutic dose of 10 to 30 mg/day was reached. Subjects were recruited into the study, which was conducted at the Schizophrenia Clinic of Stanford University School of Medicine, between January 2005 and December 2006. RESULTS: Of 15 eligible patients, 7 completed the trial. All 7 had at least minimal improvement on the YBOCS, the Clinical Global Impressions (CGI) scale, and the Positive and Negative Syndrome Scale (PANSS). At week 6, the mean CGI-Improvement scale score was 2.3 (much improved). Mean PANSS scores decreased from 75 to 56, a mean decrease of 21%, (p < .05). On the YBOCS, 6 of 7 completers showed a change of greater than 35% from baseline to week 6. CONCLUSION: These results suggest that aripiprazole monotherapy can modestly improve the outcome for some schizophrenia patients with obsessive-compulsive symptoms. Further studies with aripiprazole under controlled conditions are indicated for this population of patients. Overall, even modest improvement in global functioning due to an improvement in an OCS component may be clinically meaningful for this difficult-to-treat subset of schizophrenia patients.

Ketter TA, Brooks JO, Hoblyn JC, Champion LM, Nam JY, Culver JL, Marsh WK, Bonner JC. · Stanford University School of Medicine, 401 Quarry Road, Room 2124, Stanford, CA, USA. · J Psychiatr Res. · Pubmed #18423667 No free full text.

Abstract: OBJECTIVE: To assess lamotrigine effectiveness in bipolar disorder (BD) patients in a clinical setting. METHOD: Open lamotrigine was naturalistically administered to outpatients at the Stanford University BD Clinic assessed with the Systematic Treatment Enhancement Program for BD (STEP-BD) Affective Disorders Evaluation, and monitored longitudinally with the STEP-BD Clinical Monitoring Form. RESULTS: One hundred and ninety-seven patients (64 BD I, 110 BD II, 21 BD NOS, 2 Schizoaffective Bipolar Type, mean+/-SD age 42.2+/-14.4 years, 62% female) had 200 trials of lamotrigine. Lamotrigine was combined with a mean of 2.1+/-1.5 other psychotropic medications, most often during euthymia or depressive symptoms. Mean lamotrigine duration was 434+/-444 days, and mean final dose was 236+/-132mg/day without valproate, and 169+/-137mg/day with valproate. Lamotrigine was discontinued in only 26.5% of trials at 255+/-242 days, most often due to inefficacy, and seldom due to adverse effects. In 31.5% of trials lamotrigine was continued 264+/-375 days with no subsequent psychotropic added. In 42.0% of trials lamotrigine was continued 674+/-479 days, but had subsequent psychotropic added at 146+/-150 days, most often for anxiety/insomnia and depressive symptoms. In 145 trials started at Stanford, lamotrigine primarily yielded relief of depressive symptoms or maintained euthymia. In 55 trials in which lamotrigine was started prior to Stanford, lamotrigine primarily maintained euthymia. Lamotrigine was generally well tolerated, with no serious rash, and only 3.5% discontinuing due to benign rash. CONCLUSION: In a cohort of bipolar disorder outpatients commonly with comorbid conditions, and most often receiving complex combination therapy, lamotrigine had a low (26.5%, with an overall mean duration of treatment of 434 days) discontinuation rate, suggesting effectiveness in BD in a clinical setting.

Chang K, Saxena K, Howe M. · Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305-5540, USA. · J Am Acad Child Adolesc Psychiatry. · Pubmed #16540814 No free full text.

Abstract: OBJECTIVE: The treatment of pediatric bipolar depression has not been well studied. The authors wished to prospectively study the efficacy of lamotrigine as adjunctive or monotherapy in adolescents with bipolar disorder who were experiencing a depressive episode. METHOD: This was an 8-week open-label trial of lamotrigine with 20 adolescents ages 12-17 years (mean age 15.8; 7 boys, 13 girls) with diagnoses of bipolar disorder I, II, or not otherwise specified, who were experiencing a depressive episode. Lamotrigine was begun at 12.5 to 25 mg/day. Primary response criteria was a 1 or a 2 on the Clinical Global Impression-Improvement at week 8. A secondary criterion was at least a 50% decrease in Children's Depression Rating Scale-Revised scores. RESULTS: Nineteen subjects completed the trial. The mean final dose was 131.6 mg/day. Seven subjects were taking other psychotropic medications. Sixteen subjects (84%) responded by primary criteria, and 12 (63%) responded to our secondary criteria. Eleven subjects (58%) were considered in remission at week 8. Young Mania Rating Scale and Overt Aggression Scale-Modified scores also decreased significantly during the trial. There was no significant weight change, rash, or other adverse effects during the trial. CONCLUSIONS: Adolescents with bipolar depression appeared to respond to lamotrigine treatment, whether as adjunctive therapy or monotherapy, with decreases in depression, mania, and aggression. Larger, placebo-controlled studies of lamotrigine are needed in this population.

Koran LM, Aboujaoude E, Ward H, Shapira NA, Sallee FR, Gamel N, Elliott M. · Department of Psychiatry and Behavioral Sciences, Stanford University Medical Center, Stanford, CA 94305, USA. · J Clin Psychopharmacol. · Pubmed #16415712 No free full text.

Abstract: INTRODUCTION: Small studies have suggested that intravenous clomipramine (CMI) may be more effective and induce faster improvement in obsessive-compulsive disorder than do orally administered serotonin reuptake inhibitors. OBJECTIVE: To test these hypotheses, we conducted a randomized, double-blind, double-dummy study of pulse-loaded intravenous versus oral CMI, followed by open-label oral CMI for 12 weeks. METHODS: We enrolled a volunteer and referred group of 34 adults with a primary diagnosis of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition obsessive-compulsive disorder of > or =1-year duration and Yale-Brown Obsessive Scale score of > or =20. Eligible subjects had failed > or =2 adequate serotonin reuptake inhibitor trials. Subjects received pulse loaded CMI 150 mg by vein or by mouth on day 1 and 200 mg on day 2. Oral CMI began on day 6 at 200 mg/d and was increased by 25 mg every 4 days to 250 mg/d, as tolerated, for 12 weeks. RESULTS: Adverse events led to one withdrawal during oral pulse loading and 5 during open-label oral treatment. Intravenous pulse loading did not induce a more rapid or greater Yale-Brown Obsessive Scale score decrease than oral pulse loading at day 6 or by week 12. Day 6 and week 12 improvement were unrelated to plasma drug or metabolite concentrations. Pulse loading itself seemed to induce more rapid and greater improvement than expected in treatment-resistant obsessive-compulsive disorder. CONCLUSIONS: Further investigation of oral pulse-loading regimens in treatment-resistant obsessive-compulsive disorder is warranted.

Debattista C, Solomon A, Arnow B, Kendrick E, Tilston J, Schatzberg AF. · Depression Research Clinic, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305-5723, USA · J Clin Psychopharmacol. · Pubmed #16160625 No free full text.

Abstract: BACKGROUND: Agitation is both a feature of major depression and a common side effect of antidepressant treatment. Depressive agitation correlates with overall severity of illness and suicide risk, whereas treatment-emergent agitation may contribute to early discontinuation of pharmacotherapy. Thus, agitation merits investigation as a treatment target in clinical depression. METHODS: In this study, adults with major depression were evaluated for change in agitation and other mood symptoms during adjunctive treatment with divalproex sodium. Twelve patients on antidepressants, who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for major depression, were given low doses of divalproex sodium and evaluated repeatedly for symptoms of depression, anxiety, and agitation. Agitation severity was evaluated using the Overt Agitation Severity Scale and the Stanford Scale for Agitation Symptoms. Mood symptoms were assessed with the Hamilton Anxiety and the Hamilton Depression Rating Scales. RESULTS: Nine of 12 patients completed 4 weeks of treatment. All agitation scores decreased sharply, whereas depression (Hamilton Depression Rating Scale) and anxiety (Hamilton Anxiety Rating Scale) symptoms decreased only modestly. Decreased agitation was not merely a function of decreases on the Hamilton Depression or Hamilton Anxiety Rating Scales. Relatively low doses of divalproex sodium appear to be useful in the treatment of agitation associated with major depression. CONCLUSIONS: The observation that decreases in agitation were not simply an artifact of overall change in depressive or anxiety symptoms is in keeping with the previous clinical impression that divalproex sodium has a specific effect on depressive agitation. Controlled clinical trials are needed to fully evaluate the utility and symptom specificity of divalproex sodium in depression.

Cassidy EL, Lauderdale S, Sheikh JI. · Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, USA. · J Geriatr Psychiatry Neurol. · Pubmed #15911936 No free full text.

Abstract: The frequent comorbidity of anxiety and depression, particularly among elderly, is widely recognized by clinicians, but the debate continues as to whether the combined diagnostic designation is merited. This article reviews the debate over the mixed diagnosis, discusses treatment implications, and reviews a small treatment study undertaken with elderly patients. Ten community-dwelling, older adults diagnosed with generalized anxiety disorder and subsyndromal depression (n = 6) or generalized anxiety disorder and major depressive disorder (n = 4) were started on a 12-week, open-label trial of nefazodone. Clinicians' ratings on the Clinical Global Impression of Change and patients' self-ratings of symptoms on the Beck Depression Inventory and the Beck Anxiety Inventory identified statistically significant gains in patients' overall pre/post functioning. Nefazodone was efficacious in symptom alleviation in patients with comorbid anxiety and depression. Further double-blind, randomized investigations with newer antidepressant medications are required to extend these preliminary findings with nefazodone.

Koran LM, Gamel NN, Choung HW, Smith EH, Aboujaoude EN. · Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA. · J Clin Psychiatry. · Pubmed #15816795 No free full text.

Abstract: BACKGROUND: Many patients with obsessive-compulsive disorder (OCD) experience little response to standard treatment with serotonin reuptake inhibitors. Mirtazapine enhances serotonergic function by a mechanism distinct from reuptake inhibition. Because a pilot study suggested effectiveness of mirtazapine in OCD, we conducted a controlled trial. METHOD: We recruited 30 subjects, 15 treatmentnaive and 15 treatment-experienced, with DSM-IV OCD of > or =1 year's duration and a Yale-Brown Obsessive Compulsive Scale (YBOCS) score of > or =20. In the 12-week, open-label phase, subjects received mirtazapine starting at 30 mg/day and titrated over 2 weeks as tolerated to 60 mg/day. At week 12, responders (YBOCS score decrease > 25%) were randomly assigned, double-blind, to continue mirtazapine or switch to placebo for 8 weeks, including a 1-week, double-blind taper week for placebo subjects. RESULTS: In the open-label phase, the mean +/-SD YBOCS score fell from 28.3 +/-3.7 to 20.3 +/-8.5 (paired samples t = 4.81, p < .0001). Four subjects (13.3%) discontinued for side effects. Sixteen subjects (53.3%) (8 treatmentnaive, 8 treatment-experienced) were responders and 15 agreed to randomization. Response was independent of comorbid mood disorders. In the 8-week, double-blind, placebo-controlled discontinuation phase, the mirtazapine group's mean YBOCS score fell a mean +/-SD of 2.6 +/-8.7 points while the placebo group's mean score rose a mean +/-SD of 9.1 +/-7.5 points (Mann Whitney U = 6.5, p = .005, 1-tailed). All other outcome measures were consistent with mirtazapine's superiority versus placebo. CONCLUSION: Mirtazapine may be an effective pharmacotherapy for OCD. If our results are replicated, larger double-blind studies would be indicated.

Koran LM, Aboujaoude E, Bullock KD, Franz B, Gamel N, Elliott M. · Department of Psychiatry and Behavioral Sciences, Stanford University Medical Center, Stanford, CA 94305, USA. · J Clin Psychiatry. · Pubmed #15766302 No free full text.

Abstract: BACKGROUND: Obsessive-compulsive disorder (OCD) often responds inadequately to serotonin reuptake inhibitors (SRIs). A case series reported substantial response to once-weekly oral morphine. We conducted a placebo-controlled, double-blind trial to investigate whether once-weekly oral morphine is effective in SRI-resistant OCD. METHOD: Subjects with DSM-IV-defined OCD for > or =3 years who had failed > or =2 adequate SRI trials and had a Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score of > or =20 were recruited. Current medications were continued. Subjects were randomly assigned to random-order, 2-week blocks of once-weekly morphine, lorazepam, and placebo. Week 2 dosage was increased, decreased, or maintained depending on response and side effects. RESULTS: We enrolled 23 subjects, who had failed 2 to 6 SRI trials. The median screening Y-BOCS score was 29. The median Y-BOCS score after morphine (highest dose) was 25 (median decrease = 13%). Seven subjects (30%) were responders (Y-BOCS decreases > or =25%). The median Y-BOCS score after lorazepam (highest dose) was 27 (median decrease = 6%). Four subjects (17%) responded to lorazepam; 1 was a morphine responder. The median Y-BOCS score after placebo (highest dose) was 27 (median decrease = 7%), and no subject responded. Responses differed significantly among the 3 conditions (Friedman 2-way analysis of variance, chir(2) = 13.92, df = 2, p = .01). Wilcoxon matched-pairs signed-rank tests (T = 56.5, p = .05) showed significance for morphine versus placebo but not lorazepam versus placebo. CONCLUSION: Our results support the hypothesis that once-weekly oral morphine can reduce symptoms in some treatment-resistant OCD patients. The mechanism of action is unknown. Further studies of mu-agonists and glutamate antagonists are warranted.

Koopman C, Ismailji T, Holmes D, Classen CC, Palesh O, Wales T. · Department of Psychiatry and Behavioral Sciences, Stanford University, CA 94305, USA. · J Health Psychol. · Pubmed #15723891 No free full text.

Abstract: This study examined the effects of expressive writing on depression, posttraumatic stress disorder (PTSD) and pain symptoms among women who have survived intimate partner violence (IPV). Forty-seven women completed baseline and four-month follow-up assessments and were randomly assigned to four writing sessions of either expressive writing focused on traumatic life events or writing about a neutral topic. Main effects were not significant for changes in depression, pain or PTSD symptoms. However, among depressed women, those assigned to expressive writing showed a significantly greater drop in depression. For depressed women with IPV histories, expressive writing may lead to reduced depression.

Bogan AM, Koran LM, Chuong HW, Vapnik T, Bystritsky A. · Department of Psychiatry and Behavioral Sciences, Stanford University Medical Center, Stanford, CA 94305, USA. · J Clin Psychiatry. · Pubmed #15669891 No free full text.

Abstract: BACKGROUND: The response of obsessive-compulsive disorder (OCD) to serotonin reuptake inhibitors (SRIs) is often inadequate. Case series reporting successful augmentation with risperidone and olanzapine led us to investigate quetiapine in OCD that was resistant to SRI treatment. METHOD: In this 8-week, 2-site (S1, S2), open-label trial, 30 adults (16 at S1 and 14 at S2) with a DSM-IV diagnosis of OCD, SRI-resistant, received augmentation with quetiapine, with the dose doubled every 2 weeks from 25 mg to 200 mg/day. Primary outcome was measured with the Yale-Brown Obsessive Compulsive Scale (YBOCS). A response was defined as a > or = 25% decrease from the baseline YBOCS score. RESULTS: Significant differences between the sites in patient characteristics (7/14 at S2 were hoarders, i.e., more treatment resistant, vs. 1/16 at S1; p = .01) and in quetiapine treatment (mean +/- SD dose of 116 +/- 72 mg/day at S2 vs. 169 +/- 57 mg/day at S1; p = .039) necessitated separate analysis of results. At S1, the mean +/- SD YBOCS score fell significantly from 27.7 +/- 7.0 to 23.3 +/- 8.4 (t = 2.96, df = 15, p = .01), and the responder rate was 31% (5/16). At S2, the mean YBOCS score did not decrease significantly, and the responder rate was 14% (2/14). Most adverse medication events were mild or moderate. Two subjects (13%) at S1 and 3 (21%) at S2 withdrew due to adverse events. CONCLUSION: The results at S1 resemble those reported with other atypical antipsychotics and suggest that quetiapine augmentation may benefit treatment-resistant OCD. The poorer results at S2 may reflect the large proportion of hoarders or the less intense treatment. Longer, higher dose, large, double-blind, placebo-controlled comparison trials of atypical antipsychotics are needed.

Lembke A, Miklowitz DJ, Otto MW, Zhang H, Wisniewski SR, Sachs GS, Thase ME, Ketter TA, Anonymous00159. · Stanford University School of Medicine, CA, USA. · J Psychiatr Pract. · Pubmed #15330403 No free full text.

Abstract: OBJECTIVE: Although patients with bipolar disorder have been shown to benefit from psychosocial interventions, the proportion that utilizes these interventions is unknown. We set out to clarify the determinants of psychosocial service utilization in adults with bipolar disorder. METHOD: We investigated psychosocial service utilization among the first 500 patients admitted to the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). RESULTS: In the 3 months prior to enrollment in STEP-BD, a majority of the patients (54%) were engaged in at least one psychosocial service modality in addition to pharmacotherapy. In order of decreasing frequency, these were therapy with a psychologist, self-help group, therapy with a social worker, and therapy with another type of provider. Bipolar patients with personality disorders (80% vs 20%, p = 0.0002), alcohol/drug abuse disorders (76% vs 24%, p = 0.0022), and anxiety disorders (60% vs 40%, p = 0.0043) received more psychosocial services than those without. Poorer global functioning also increased the likelihood of receiving services, whereas being married decreased service utilization. CONCLUSION: Psychosocial service utilization by outpatients with bipolar disorder is strongly linked to greater severity/complexity of illness. Potential moderators, such as insurance status and availability of care, should be examined in future studies.

Frayne SM, Seaver MR, Loveland S, Christiansen CL, Spiro A, Parker VA, Skinner KM. · Center for Health Care Evaluation, Veterans Affairs Palo Alto Health Care System, Menlo Park, Calif, USA. · Arch Intern Med. · Pubmed #15226164 links to  free full text

Abstract: BACKGROUND: Depression and posttraumatic stress disorder (PTSD) are important women's health issues. Depression is known to be associated with poor physical health; however, associations between physical health and PTSD, a common comorbidity of depression, have received less attention. OBJECTIVES: To examine number of medical symptoms and physical health status in women with PTSD across age strata and benchmark them against those of women with depression alone or with neither depression nor PTSD. METHODS: A random sample of Veterans Health Administration enrollees received a mailed survey in 1999-2000 (response rate, 63%). The 30 865 women respondents were categorized according to whether a health care provider had ever told them that they had PTSD, depression (without PTSD), or neither. Outcomes were self-reported medical conditions and physical health status measured with the Veterans SF-36 instrument, a version of the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) modified for use in veteran populations. RESULTS: Across age strata, women with PTSD (n = 4348) had more medical conditions and worse physical health status (physical functioning, role limitations due to physical problems, bodily pain, and energy/vitality scales from the Veterans SF-36) than women with depression alone (n = 7580) or neither (n = 18 937). In age-adjusted analyses, the Physical Component Summary score was on average 3.4 points lower in women with depression alone and 6.3 points lower in women with PTSD than in women with neither (P<.001). CONCLUSIONS: Posttraumatic stress disorder is associated with a greater burden of medical illness than is seen with depression alone. The presence of PTSD may account for an important component of the excess medical morbidity and functional status limitations seen in women with depression.

Glick ID, Zaninelli R, Hsu C, Young FK, Weiss L, Gunay I, Kumar V. · Stanford University School of Medicine, Stanford, California, USA. · J Clin Psychiatry. · Pubmed #15163255 No free full text.

Abstract: BACKGROUND: Results from the International Suicide Prevention Trial (InterSePT) indicate that clozapine is more effective than olanzapine in reducing suicidal behavior in schizophrenic and schizoaffective patients. However, because InterSePT allowed the uncontrolled use of concomitant psychotropic medications (CPMs), it is possible that the antisuicidal effect of clozapine may have been influenced by greater use of such agents. This article describes the use patterns of CPMs during InterSePT and examines whether CPM use may have affected study outcome. METHOD: In this study, 479 patients received clozapine and 477 patients received olanzapine. Concomitant psychotropic medications were grouped into 4 classes: antipsychotics, antidepressants, sedatives/anxiolytics, and mood stabilizers. The doses of each CPM were converted into dosage equivalents of standard reference drugs. An analysis of covariance was performed to compare mean daily doses of CPMs between the 2 groups over the 2-year treatment period. The duration of treatment for each patient was 2 years, with the first patient entering the study in March 1998 and the last patient completing treatment in February 2001. RESULTS: Approximately 90% of patients in both treatment groups received at least 1 CPM. The mean +/- SD number of CPMs per patient was 3.8 +/- 2.90 in the clozapine group and 4.2 +/- 3.16 in the olanzapine group. For each CPM class, the mean daily dose was statistically significantly lower in the clozapine group (antipsychotics, p <.001; antidepressants, p <.01; sedatives/anxiolytics, p <.001; mood stabilizers, p <.05). Analyses of CPM use by study intervals, suicide attempters versus nonattempters, study completers versus noncompleters, and geographic region resulted in similar findings. CONCLUSION: The results support the conclusion that the effects of clozapine in reducing the risk of suicidal behavior derive from its intrinsic pharmacology and not from the influence of concomitant psychotropic medications.

Mauss IB, Wilhelm FH, Gross JJ. · Department of Psychology, Stanford University, Stanford, California 94305-2130, USA. · Psychophysiology. · Pubmed #14570172 No free full text.

Abstract: Growing evidence suggests that, contrary to expectation, high trait socially anxious (HTSA) and low trait socially anxious (LTSA) individuals show comparable autonomic reactivity during stressful speech tasks. To test the hypothesis that autonomic differences between groups might emerge during recovery or habituation, 35 HTSA and LTSA participants gave two impromptu speeches. Measures of anxiety experience as well as cardiovascular, electrodermal, respiratory, and vagal activation were obtained. Despite greater reports of anxiety experience in the HTSA versus the LTSA participants, autonomic measures showed comparable reactivity, habituation, and recovery in the two anxiety groups. These results suggest minimal autonomic differences between HTSA and LTSA individuals, thus supporting theories of social anxiety that emphasize cognitive factors.

Koran LM, Chuong HW, Bullock KD, Smith SC. · Department of Psychiatry and Behavioral Sciences, Stanford University Medical Center, Calif., USA. · J Clin Psychiatry. · Pubmed #12934980 No free full text.

Abstract: BACKGROUND: Open-label trials suggested that fluvoxamine and citalopram may be effective for compulsive shopping disorder, but 2 double-blind fluvoxamine trials failed to confirm this. To test the hypothesis that citalopram is a safe, effective treatment for this disorder, we conducted a 7-week, open-label trial followed by a 9-week, double-blind, placebo-controlled discontinuation trial. METHOD: From Jan. 2001 to Jan. 2002, we enrolled adult outpatients meeting diagnostic criteria suggested in a prior study for compulsive shopping disorder and having a score of >/= 17 on the Yale-Brown Obsessive Compulsive Scale-Shopping Version (YBOCS-SV). Open-label citalopram was started at 20 mg/day and increased, absent marked response and limiting side effects, to 60 mg/day. Responders (subjects rated "much improved" or "very much improved" on the Clinical Global Impressions-Improvement scale [CGI-I] and having a >/= 50% decrease in YBOCS-SV score) were randomized to double-blind citalopram treatment at the week 7 dose or placebo for 9 weeks. RESULTS: We enrolled 24 subjects (23 women and 1 man). Mean +/- SD YBOCS-SV scores decreased significantly from 24.3 +/- 4.6 at baseline to 8.2 +/- 8.1 at week 7 (Wilcoxon signed rank: z = 4.20, p <.001). Fifteen of 24 subjects (63%) met the responder criteria. Three subjects (13%) discontinued for adverse events (1 each for headache, rash, and insomnia). Of the 15 responders who entered the double-blind treatment phase, 5 of 8 (63%) randomized to placebo relapsed (YBOCS-SV score >/= 17 and "minimally improved" or less on the CGI-I) compared with none of 7 randomized to continue taking citalopram (Fisher exact test p =.019). CONCLUSION: Citalopram appears to be a safe and effective treatment for compulsive shopping disorder. Further trials of citalopram and other selective serotonin reuptake inhibitors are warranted.