The impact of education, country, race and ethnicity on the self-report of postpartum depression using the Edinburgh Postnatal Depression Scale.

BACKGROUND: Universal screening for postpartum depression is recommended in many countries. Knowledge of whether the disclosure of depressive symptoms in the postpartum period differs across cultures could improve detection and provide new insights into the pathogenesis. Moreover, it is a necessary step to evaluate the universal use of screening instruments in research and clinical practice. In the current study we sought to assess whether the Edinburgh Postnatal Depression Scale (EPDS), the most widely used screening tool for postpartum depression, measures the same underlying construct across cultural groups in a large international dataset. METHOD: Ordinal regression and measurement invariance were used to explore the association between culture, operationalized as education, ethnicity/race and continent, and endorsement of depressive symptoms using the EPDS on 8209 new mothers from Europe and the USA. RESULTS: Education, but not ethnicity/race, influenced the reporting of postpartum depression [difference between robust comparative fit indexes (∆*CFI) 0.01), but not between European countries (∆*CFI < 0.01). CONCLUSIONS: Investigators and clinicians should be aware of the potential differences in expression of phenotype of postpartum depression that women of different educational backgrounds may manifest. The increasing cultural heterogeneity of societies together with the tendency towards globalization requires a culturally sensitive approach to patients, research and policies, that takes into account, beyond rhetoric, the context of a person's experiences and the context in which the research is conducted.

A double-blind, placebo-controlled study of risperidone addition in serotonin reuptake inhibitor-refractory obsessive-compulsive disorder.

BACKGROUND: To date, only 1 controlled study has found a drug (haloperidol) to be efficacious in augmenting response in patients with obsessive-compulsive disorder (OCD) refractory to serotonin reuptake inhibitor (SRI) monotherapy; patients with comorbid chronic tic disorders showed a preferential response. This report describes the first controlled study of risperidone addition in patients with OCD refractory to treatment with SRI alone. METHODS: Seventy adult patients with a primary DSM-IV diagnosis of OCD received 12 weeks of treatment with an SRI. Thirty-six patients were refractory to the SRI and were randomized in a double-blind manner to 6 weeks of risperidone (n = 20) or placebo (n = 16) addition. Behavioral ratings, including the Yale-Brown Obsessive Compulsive Scale, were obtained at baseline and throughout the trial. Placebo-treated patients subsequently received an identical open-label trial of risperidone addition. RESULTS: For study completers, 9 (50%) of 18 risperidone-treated patients were responders (mean daily dose, 2.2 +/-0.7 mg/d) compared with 0 of 15 in the placebo addition group (P<. 005). Seven (50%) of 14 patients who received open-label risperidone addition responded. Risperidone addition was superior to placebo in reducing OCD (P<.001), depressive (P<.001), and anxiety (P =.003) symptoms. There was no difference in response between OCD patients with and without comorbid diagnoses of chronic tic disorder or schizotypal personalty disorder. Other than mild, transient sedation, risperidone was well tolerated. CONCLUSION: These results suggest that OCD patients with and without comorbid chronic tic disorders or schizotypal personality disorder may respond to the addition of low-dose risperidone to ongoing SRI therapy.

Effects of catecholamine depletion with AMPT (alpha-methyl-para-tyrosine) in obsessive-compulsive disorder.

BACKGROUND: Several lines of evidence suggest that brain dopamine function may contribute to some obsessive-compulsive (OC) phenomena. The effects of catecholamine depletion were examined in drug-free patients with obsessive-compulsive disorder (OCD). METHODS: The tyrosine hydroxylase inhibitor alpha-methyl-para-tyrosine (AMPT) and diphenhydramine hydrochloride (placebo) were administered for three consecutive days, one week apart, to 6 drug-free adult OCD patients without a personal or family history of chronic tics, in a double-blind, randomized design. The effects of AMPT and placebo on OC, depression, anxiety and global clinical symptoms were assessed. RESULTS: AMPT produced no clinically or statistically significant change in any behavioral ratings, including OC symptom severity, compared with placebo. CONCLUSIONS: Acute reduction of catecholamine levels does not seem to affect OC symptoms in drug-free patients with OCD. Studies of catecholamine depletion with AMPT in patients with comorbid OCD and chronic tics may be of considerable neurobiological and clinical interest.

Olanzapine addition in obsessive-compulsive disorder refractory to selective serotonin reuptake inhibitors: an open-label case series.

BACKGROUND: Despite the efficacy of selective serotonin reuptake inhibitors (SSRIs) in the treatment of obsessive-compulsive disorder, a significant number of patients show no or only partial remission of symptoms. Some evidence exists to suggest that risperidone augmentation can be helpful in treating this refractory group. The efficacy of other atypical antipsychotic agents, such as olanzapine, in augmenting SSRIs in refractory obsessive-compulsive patients has yet to be systematically investigated. METHOD: A series of 10 patients with DSM-IV obsessive-compulsive disorder showing significant residual symptoms following an adequate SSRI trial (12 weeks) were given open-label olanzapine augmentation for a minimum of an additional 8 weeks. Treatment response was assessed using the Yale-Brown Obsessive Compulsive Scale and the Clinical Global Impressions scale. RESULTS: Nine of the 10 patients in this series treated with olanzapine and an SSRI completed the 8-week augmentation trial. Of these, 4 demonstrated a complete remission or major improvement in obsessive-compulsive symptoms, 3 had partial remission, and 2 experienced no benefit. Nine patients experienced minimal adverse effects, primarily sedation, which did not interfere with continuing treatment. One patient discontinued olanzapine owing to excessive sedation. CONCLUSION: The results of this preliminary, open-label trial suggest that olanzapine may be effective in augmenting ongoing SSRI treatment for a portion of patients with obsessive-compulsive disorder refractory to SSRI treatment. Larger, placebo-controlled trials appear warranted to investigate the clinical efficacy and tolerability of olanzapine augmentation of SSRI treatment in SSRI-refractory obsessive-compulsive disorder.

Risperidone addition in fluvoxamine-refractory obsessive-compulsive disorder: three cases.

BACKGROUND: Forty percent to 60% of patients with obsessive-compulsive disorder (OCD) remain unimproved after adequate treatment with serotonin uptake inhibitors (SUIs). The addition of low-dose haloperidol and pimozide to ongoing SUI treatment has been shown to be effective in up to 65% of SUI-refractory OCD patients, particularly in those with comorbid chronic tic disorder. Because OCD patients typically require prolonged pharmacotherapy, they are subject to the development of tardive dyskinesia during neuroleptic treatment. Risperidone is a highly potent and selective serotonin2 and dopamine2 receptor antagonist with a side effect profile that appears to be much more tolerable and safer than that of typical neuroleptics. METHOD: We report our experience with three OCD patients who were unimproved after a minimum of 12 weeks of treatment with the potent and selective SUI fluvoxamine, in whom we added risperidone in an open-label manner. RESULTS: All three patients showed significant improvement in their obsessive-compulsive symptoms as measured by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) after risperidone 1 mg/day was added to ongoing fluvoxamine (250-300 mg/day). Within 4 weeks of adding risperidone, the three patients' Y-BOCS scores had decreased by 65%, 56%, and 43%, respectively. Other than mild or moderate sedation, no side effects were observed. CONCLUSION: These results suggest that risperidone addition to ongoing SUIs may be an effective treatment strategy for refractory OCD.

A risk-benefit assessment of drugs used in the management of obsessive-compulsive disorder.

Established efficacy and tolerability in large multicentre controlled studies have made serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SRIs) the mainstay of monotherapy for adult obsessive-compulsive disorder (OCD). When compared with the selective serotonin reuptake inhibitors (SSRIs), the tricyclic compound clomipramine has a higher incidence of adverse effects but is well tolerated by most OCD patients and may confer the best overall antiobsessional effects. Consideration of specific adverse effect profiles, special patient population characteristics, drug interactions and relative cost of the various agents may direct clinicians in choosing the most appropriate first-line drug. Alternative agents as monotherapies have been explored, but none has consistently proven effective to date. Investigations of SRI augmentation with serotonin-enhancing agents have also failed to demonstrate substantial benefits for treatment-refractory OCD. Combination treatment with SRIs and dopamine receptor antagonist drugs appears to provide an improved response for the subpopulation of OCD patients who have comorbid 'tic-spectrum' disorders, though large-scale studies of the efficacy and tolerability of these regimens are not yet available.

Risperidone addition in serotonin reuptake inhibitor-resistant trichotillomania: three cases.

Open-label addition of a low-dose typical (pimozide) neuroleptic was shown to be beneficial in some patients with serotonin reuptake inhibitor (SRI)-refractory trichotillomania (TTM). Risperidone's potentially more benign acute and long-term side effect profile makes it a candidate for investigation in the treatment of TTM. We report our experience with the systematic addition of open-label risperidone 0.5 to 3 mg/day in three patients with SRI-refractory TTM. All three patients had a robust decrease in hair pulling as measured by clinician-rated instruments. These results suggest that risperidone addition to ongoing treatment with SRIs may be an effective treatment strategy for patients with SRI-refractory TTM.

Postpartum major depression: detection and treatment.

Postpartum major depression occurs in approximately one of 10 childbearing women and is considerably underdiagnosed. If left untreated, the disorder can have serious adverse effects on the mother and her relationship with significant others, and on the child's emotional and psychologic development. A simple screening instrument can be used to increase the detection of postpartum major depression. Although few well-controlled studies have been done to support the use of any one modality, the mainstay of treatment has been antidepressant therapy, alone or in combination with psychotherapy. Plasma concentrations of antidepressant drugs are usually low in the breast-fed infant, and most studies demonstrate that certain antidepressants can be used during lactation without any important adverse effects on the infant.

Gonadal steroids in the treatment of mood disorders.

UNLABELLED: Increased interest in the complex interplay between gonadal steroids and neurotransmitter systems involved in mood has led investigators to question the role of gonadal steroids in the treatment of affective disorders, especially in women. OBJECTIVES: The purpose of this article is to provide a rationale for using gonadal hormones in the treatment of depression in women. METHODS: The literature is reviewed regarding 1) sex-specific phenomenologic and epidemiologic differences in the manifestation of psychiatric illness, 2) sex-specific differences in the therapeutic and adverse effects of psychotropic medications, 3) the complex interplay between gonadal steroids and neurotransmitter systems implicated in psychiatric disorders, and 4) the growing literature regarding the use of estrogen and progesterone in the treatment of mood disorders in women and androgens in the treatment of depression and sexual dysfunction in both men and women. RESULTS: Findings from pharmacologic trials of estrogen and androgens are encouraging, albeit mixed, in the treatment of mood disorders and decreased libido in women, respectively. Controlled studies have failed to confirm early open-label reports of the effectiveness of progesterone in the treatment of premenstrual syndrome. CONCLUSIONS: Pending replication, estrogen may become an important pharmacologic agent in the treatment of postnatal and perimenopausal depression, whereas androgens have been shown to improve libido in postmenopausal women and hypogonadal men. Progesterone cannot be recommended as a treatment for premenstrual syndrome or postnatal depression.

Evidence for linkage disequilibrium between serotonin transporter protein gene (SLC6A4) and obsessive compulsive disorder.

Obsessive compulsive disorder (OCD) is characterized by recurrent and intrusive thoughts that are distressing (obsessions) and/or repetitive behaviors or mental acts that the person feels driven to perform (compulsions). OCD has a partly genetic basis. For treatment of OCD, potent serotonin reuptake inhibitor (SRI) drugs (clomipramine (Anafranil), fluvoxamine (Luvox), fluoxetine (Prozac), sertraline (Zoloft), and paroxetine (Paxil)), which act on the serotonin transporter protein, are uniquely efficacious. A polymorphism in the promoter region of the gene (SLC6A4) encoding this protein, was recently reported to affect protein expression and to be associated with measures of anxiety and depression and with autism (using a family-controlled transmission disequilibrium test (TDT) design). SLC6A4 therefore has strong a priori support for potentially influencing risk for OCD: the protein it encodes is a medication target; a polymorphism in the gene affects function; and that polymorphism has been shown to be associated with behavioral phenotypes. We used the TDT with a set of 34 European-American family trios, 30 unrelated and four drawn from an extended pedigree, to test for linkage disequilibrium between OCD and alleles at the SLC6A4 promoter polymorphic locus. Of 35 heterozygous parents, 24 transmitted the 'l' SLC6A4 allele and 11 transmitted the 's' allele (chi 2 TDT = 4.83; P < 0.03). Considering only the 13 SRI drug nonresponders, there were 13 heterozygous parents, of whom 10 transmitted the 'l' allele and three the 's' allele (chi 2 TDT = 3.77; P < 0.052). These data provide preliminary support for association and linkage disequilibrium between the SLC6A4 'l' allele and OCD.

Glutamate and GABA systems as targets for novel antidepressant and mood-stabilizing treatments.

Glutamate and gamma-amino butyric acid (GABA) systems are emerging as targets for development of medications for mood disorders. There is increasing preclinical and clinical evidence that antidepressant drugs directly or indirectly reduce N-methyl-D-aspartate glutamate receptor function. Drugs that reduce glutamatergic activity or glutamate receptor-related signal transduction may also have antimanic effects. Recent studies employing magnetic resonance spectroscopy also suggest that unipolar, but not bipolar, depression is associated with reductions in cortical GABA levels. Antidepressant and mood-stabilizing treatments also appear to raise cortical GABA levels and to ameliorate GABA deficits in patients with mood disorders. The preponderance of available evidence suggests that glutamatergic and GABAergic modulation may be an important property of available antidepressant and mood-stabilizing agents. Future research will be needed to develop and evaluate new agents with specific glutamate and GABA receptor targets in the treatment of mood disorders.