Translating the evidence on atypical depression into clinical practice.
ABSTRACT Although the introduction of selective serotonin reuptake inhibitors ushered in an era of relative comfort among clinicians in treating major depressive disorder (MDD), no one antidepressant is appropriate for all patients with depression. In patients with atypical symptoms, efficacy of therapeutic agents may be greatest for monoamine oxidase inhibitors (MAOIs). The first-generation MAOIs such as phenelzine and isocarboxazid were largely nonselective inhibitors of both subtypes of MAO, MAO(A) and MAO(B). These medications carried with them dietary restrictions, medication restrictions, a need for titration, and a substantial side effect burden, including weight gain, cardiovascular effects (i.e., hypertension and hypotension), and sexual side effects. The second-generation MAOI selegiline is selective for MAO(B) at oral doses of up to 10 mg/day. At higher doses, selegiline loses selectivity and inhibits both MAO(A) and MAO(B). Because the antidepressant effects of selegiline occur with the higher doses that impact tyramine pressor effects, an ideal formulation would optimize dose while minimizing adverse effects of MAO(A) inhibition in the gastrointestinal mucosa. Efforts in this direction led to formulation of the selegiline transdermal system (STS). The most common side effects are irritation at the patch site and insomnia. Drugs to be avoided with the STS include some pain medications, antidepressants, muscle relaxants, and any form of sympathomimetic amines, which include amphetamines, cold products with pseudoephedrine, phenylephrine, phenylpropanolamine, ephedrine, and stimulant-containing weight-reduction agents. Although no tyramine-restricted diet is required for the 6-mg/24-hour patch, a restricted diet is recommended for the higher-dose patches to reduce the risk of hypertensive crisis.
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ABSTRACT: It is often assumed that individual stigmatizing attitudes toward the mentally ill are linked to stigmatizing attitudes in the social milieu and that both, individual and social stigmatizing attitudes are major barriers to mental health treatment seeking. This study aims to examine these assumptions. Data from the 2005-2006 Eurobarometer general population survey (N = 29,248) are used to examine the association of social stigmatizing attitudes assessed in a random half of the sample with individual stigmatizing attitudes assessed in the other half of the sample, and to examine the association of both individual and social stigmatizing attitudes with willingness to seek professional help. Social stigmatizing attitudes are specifically and strongly associated with individual stigmatizing attitudes. Both social and individual stigmatizing attitudes are associated with willingness to seek professional help. Believing the mentally ill to be dangerous or not likely to recover, or living in a community with such beliefs, are associated with increased willingness to seek help; whereas, believing the mentally ill to be unpredictable or blameworthy for their illness, or living in a community with strong beliefs in blameworthiness of the mentally ill, are associated with decreased willingness to seek professional help. The view that all stigmatizing attitudes toward mental illness are associated with reluctance to seek professional help may be naive as some stigmatizing attitudes may be associated with increased willingness to seek help. The complex association of different stigmatizing attitudes with professional help seeking should be carefully considered in planning anti-stigma campaigns.Social Psychiatry 09/2009; 45(7):705-12. DOI:10.1007/s00127-009-0109-2 · 2.58 Impact Factor
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ABSTRACT: Activity of the hypothalamic-pituitary-adrenocortical (HPA) axis is often abnormal in depression and could hold clues for better treatment of this debilitating disease. However, it has been difficult to use HPA activity as a depression biomarker because both HPA hyperactivity and HPA hypoactivity have been reported in depression. Melancholic depression has typically been associated with HPA hyperactivity, while atypical depression has been linked with HPA hypoactivity. Many animal models of chronic stress recapitulate behavioral aberrations and elevated HPA activity that could represent a model for melancholic depression. However, there are no animal models that could be used to elucidate the etiology or treatment of atypical depression. We have used repeated social defeat in mice to test the hypothesis that this chronic stress would induce dysphoria-like behavior associated with HPA hypoactivity in a subset of subjects. Intruder mice were placed in the home cage of an aggressive resident mouse for 5 min/d for 30 days. The majority of intruder mice had elevated basal plasma corticosterone (High Morning Corticosterone, or HMC) and adrenal 11β hydroxylase mRNA levels relative to control mice that were handled daily. However, a subset of intruder mice (Low Morning Corticosterone; LMC) exhibited basal plasma corticosterone and 11β hydroxylase mRNA levels that were indistinguishable from control levels. Significant changes in emotional behavior only occurred in LMC mice, which exhibited anxiety-like increases in activity and defecation during tail suspension and anhedonia-like decreases in sucrose preference. Relative to HMC mice, LMC mice also showed increases in gene expression of mineralocorticoid receptor in CA2 hippocampus, consistent with the possibility that HPA activity in this group is constrained by increased sensitivity to glucocorticoid negative feedback. LMC mice also exhibited increased c-fos gene expression compared to HMC mice in the paraventricular hypothalamus and lateral septum suggesting that central pathways fail to habituate to chronic stress even though adrenocortical activity is not stimulated. We conclude that LMC mice showed adrenocortical hyporesponsiveness, which in combination with the behavioral abnormalities in this group may represent a model for the HPA hypoactivity associated with atypical depression.Physiology & Behavior 11/2011; 105(4):958-65. DOI:10.1016/j.physbeh.2011.10.032 · 3.03 Impact Factor
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ABSTRACT: Despite several decades of research, the characteristics distinguishing atypical depression from other depressive subtypes remain ambiguous. Multiple lines of evidence support the designation of atypical depression as a scientifically and clinically relevant subtype, including differences in hormonal responses, brain laterality, psychological profile and psychiatric co-morbidity and differential treatment response. The evolution of the diagnostic criteria for atypical depression has led to the designation of mood reactivity as the cardinal feature, and the research supporting this conclusion is reviewed. This paper also reviews the evidence for the drug treatment of atypical depression, with a particular focus on research related to the superior efficacy of monoamine oxidase inhibitors (MAOIs) compared with tricyclic antidepressants (TCAs). Data relevant to the efficacy of newer antidepressants, including selective serotonin reuptake inhibitors (SSRIs), serotonin-noradrenaline (norepinephrine) reuptake inhibitors, transdermal selegiline and other new agents for atypical depression, are discussed. In summary, the diagnostic reliability and validity of atypical depression still remain elusive and open to further evolution. Currently available findings suggest that atypical depression has preferential response to MAOIs over TCAs. More data are required to determine the efficacy of newer agents relative to MAOIs and TCAs, although limited studies have shown a non-inferior efficacy and better tolerability of newer agents such as SSRIs compared with those of MAOIs and TCAs. Finally, future directions for research include further refinement of the diagnostic criteria for atypical depression, and clarification of the role of newer antidepressants in the treatment of this subtype with evidence from randomized, controlled trials.CNS Drugs 12/2009; 23(12):1023-37. DOI:10.2165/11310990-000000000-00000 · 4.38 Impact Factor