Despite the development of several effective treatments for depression, symptoms often persist in a number of individuals. Unfortunately, these residual symptoms are associated with several negative outcomes, including persistence of depressive illness. Few studies have examined the exact nature of individual residual symptoms across specific treatment modalities, and studies have failed to distinguish between depression courses. The current study expands on previous findings by examining, among a chronically depressed population, differences in individual residual symptoms and clusters between treatment modality (medication, psychotherapy, combination) and treatment response (full response, partial response). Five hundred and nineteen chronically depressed participants completed the study. Participants were randomly assigned to receive treatment with nefazodone, CBASP, or the combination of both. Residual symptoms were assessed with two depression severity ratings, a clinician administered interview and a self-report questionnaire. The frequency and severity of individual residual symptoms and clusters were examined between treatment and response groups. The emergence of symptoms after treatment was compared between treatment groups. Residual symptoms were common, reported in over 90% of the sample. The most common residual symptoms reflected both core depressive symptoms and co-morbid symptoms not specific to depression. In general, similar residual symptoms were reported among partial and full responders. The only individual residual symptoms that differed between treatment groups were early insomnia, OCD symptoms, hopelessness, hypersomnia, concentration, and decreased libido. Treatment groups also differed on two factors of the HDRS. The Nefazodone group reported a greater number of Disturbed Thinking items than the CBASP group. The CBASP group reported more items on the Psychic Depression factor compared to the Nefazodone group for full responders only. Analyses revealed that the Nefazodone group was more likely to report the emergence of guilt and psychic anxiety after treatment than the CBASP and Combination group, and the emergence of weight loss occurred more frequently among participants in the Nefazodone and Combination groups when compared with the CBASP group. Results suggest residual weight loss may be a side effect of medication and CBASP may offer protection against the development of guilt and anxiety.

We report on 3 subjects with premenstrual magnification of major depression (PMMD) treated with nefazodone who benefited from a supplement of additional nefazodone premenstrually. During the 6-month study, subjects were given supplements of either additional nefazodone or placebo prior to the expected onset of menses (double-blind crossover design). Symptoms were assessed during the late luteal and follicular phases. All subjects showed significant improvement for the months in which they received nefazodone supplements, but not when given placebo. Premenstrual dose increase is a clinically promising intervention for women who experience PMMD.

<p>Premenstrual dysphoria, so severe that it affects the lives of the women afflicted, is the condition studied in this thesis. Physiological and pharmacological mechanisms of pathogenetic relevance were investigated. </p><p>Women with premenstrual dysphoria showed a stronger and less dampened response of LH to an estradiol challenge than asymptomatic women, indicating an altered neuroendocrine regulation. In women with premenstrual dysphoria, the LH response was correlated to the severity of irritability and bloating, and the early FSH response was correlated to the severity of depressed mood. </p><p>The positron-emission study showed strong, consistent correlations between worsening of mood symptoms and a decrease in brain trapping of the immediate serotonin precursor, from the mid-follicular to the late luteal phase in women with premenstrual dysphoria. The strongest correlations were seen for the cardinal mood symptoms of premenstrual dysphoria, and for their opposites. Physical symptoms showed weaker or no correlations with the exception of nociceptive symptoms from erogenous body regions which showed positive correlations to serotonin precursor trapping in the right caudate nucleus. The findings are consistent with the serotonin hypothesis of premenstrual dysphoria, and might possibly explain the observed effects of serotonin-augmenting drugs in this condition.</p><p>The partial 5-HT_1A receptor agonist buspirone was superior to placebo in the treatment of premenstrual dysphoria. The weak SRI and 5-HT₂ receptor antagonist nefazodone was not superior to placebo. For women with premenstrual dysphoria in need of medication and who do not tolerate SRIs because of the sexual sideeffects, buspirone may be an alternative drug, since it had no adverse effects on sexual function. </p><p>The prevalence of polycystic ovaries and serum levels of androgens were not higher in women with premenstrual dysphoria than in their asymptomatic counterparts. The findings are not consistent with the hypothesis that irritability in women with premenstrual dysphoria is induced by elevated testosterone levels. </p><p>Thesis results, which are in line with the serotonin hypothesis of premenstrual dysphoria, may imply that increased brain sensitivity is one of the factors underlying severe premenstrual mood symptoms, thereby further supporting a common serotonergic dysregulation in this condition.</p>

Premenstrual dysphoria, so severe that it affects the lives of the women afflicted, is the condition studied in this thesis. Physiological and pharmacological mechanisms of pathogenetic relevance were investigated. Women with premenstrual dysphoria showed a stronger and less dampened response of LH to an estradiol challenge than asymptomatic women, indicating an altered neuroendocrine regulation. In women with premenstrual dysphoria, the LH response was correlated to the severity of irritability and bloating, and the early FSH response was correlated to the severity of depressed mood. The positron-emission study showed strong, consistent correlations between worsening of mood symptoms and a decrease in brain trapping of the immediate serotonin precursor, from the mid-follicular to the late luteal phase in women with premenstrual dysphoria. The strongest correlations were seen for the cardinal mood symptoms of premenstrual dysphoria, and for their opposites. Physical symptoms showed weaker or no correlations with the exception of nociceptive symptoms from erogenous body regions which showed positive correlations to serotonin precursor trapping in the right caudate nucleus. The findings are consistent with the serotonin hypothesis of premenstrual dysphoria, and might possibly explain the observed effects of serotonin-augmenting drugs in this condition. The partial 5-HT1A receptor agonist buspirone was superior to placebo in the treatment of premenstrual dysphoria. The weak SRI and 5-HT2 receptor antagonist nefazodone was not superior to placebo. For women with premenstrual dysphoria in need of medication and who do not tolerate SRIs because of the sexual sideeffects, buspirone may be an alternative drug, since it had no adverse effects on sexual function. The prevalence of polycystic ovaries and serum levels of androgens were not higher in women with premenstrual dysphoria than in their asymptomatic counterparts. The findings are not consistent with the hypothesis that irritability in women with premenstrual dysphoria is induced by elevated testosterone levels. Thesis results, which are in line with the serotonin hypothesis of premenstrual dysphoria, may imply that increased brain sensitivity is one of the factors underlying severe premenstrual mood symptoms, thereby further supporting a common serotonergic dysregulation in this condition.