Relapse during a 6-month continuation treatment with fluvoxamine in an Italian population: the role of clinical, psychosocial and genetic variables.

The efficacy of SSRIs in relapse prevention in major depression has been extensively demonstrated. Considering published data, the relapse rate during a psychopharmacological continuation treatment ranges from 10% to 30%. Since the reasons of depressive relapses could be heterogeneous, we have tested the effect of clinical, psychosocial and genetic variables in sustained remission from an index depressive episode during continuation treatment with fluvoxamine over a 6-month follow-up period. 101 patients maintained the same full dosage treatment after remission from a depressive episode efficaciously treated with fluvoxamine. During the follow-up period, they were clinical assessed monthly by an experienced psychiatrist and SASS was administered, to assess their psychosocial adjustment. From a genetical point of view, SERTPR and CLOCK polymorphisms were analyzed for each patients, using PCR-based techniques. At the end of follow-up period, the 57.4% of the patients maintained remission during fluvoxamine continuation treatment; the 8.9% relapsed within the first 2 months of continuation; the 7.9% switched and the 25.8% dropped-out for poor compliance. Relapsed subjects presented a significantly longer mean duration of the index depressive episode than non-relapsed subjects and a subjective poor social adjustment than non-relapsed also in the euthymia period. None of the analyzed polymorphisms significantly appear to influence the outcome of the whole sample. The present data confirm that patients with severe depression and a long duration of the episode have a major risk of psychosocial disability. These patients could need a different psychopharmacological strategies and peculiar psychological intervention.

Dark therapy for mania: a pilot study.

BACKGROUND: Recent findings suggest that extended bed rest and darkness could stabilize mood swings in rapid cycling bipolar patients. METHOD: We exposed 16 bipolar inpatients affected by a manic episode to a regimen of 14 h of enforced darkness from 6 p.m. to 8 a.m. each night for three consecutive days [dark therapy (DT)]. Pattern of mood changes were recorded with the Young Mania Rating Scale (YMRS) and compared with a control group of 16 inpatients matched for age, sex, age at onset, number of previous illness episodes and duration of current episode, and were treated with therapy as usual (TAU). RESULTS: Adding DT to TAU resulted in a significantly faster decrease of YMRS scores when patients were treated within 2 weeks from the onset of the current manic episode. When duration of current episode was longer, DT had no effect. Follow-up confirmed that good responders needed a lower dose of antimanic drugs and were discharged earlier from the hospital. CONCLUSIONS: Chronobiological interventions and control of environmental stimuli can be a useful add-on for the treatment of acute mania in a hospital setting.

Pharmacogenetics of selective serotonin reuptake inhibitor response: a 6-month follow-up.

BACKGROUND: We previously reported the association between some genetic factors and short-term antidepressant outcome. In the present paper we investigated the same gene variants in a prospective 6-months naturalistic follow-up. METHODS: The sample included 185 inpatients affected by recurrent major depression consecutively admitted to the Psychiatric Inpatient Unit of San Raffaele Hospital from 1998 to 2003 and prospectively followed for 6 months after their recovery. All the patients were undertaking continuation therapy. The functional polymorphism in the upstream regulatory region of the serotonin transporter gene (SERTPR), the tryptophan hydroxylase A218C substitution, a VNTR polymorphism located 1.2 kb upstream of the monoamine oxidase-A coding sequences, the CLOCK gene T3111C and the PER3exon15 gene T1940G substitutions were analysed, using PCR-based techniques. RESULTS: No association was found between clinical variables and relapses; subjects showing TT genotype at CLOCK gene tended to relapse within 6 months after recovery more than TC and CC subjects taken together. A non-significant tendency of SERTPR*s/s subjects to a minor frequency of relapse was also observed. CONCLUSION: Some subjects showing remission after acute treatment relapsed within 6 months, despite undertaking a maintenance treatment; the causes could be heterogeneous, but CLOCK gene variants may influence the outcome.

Migraine headache and mood disorders: a descriptive study in an outpatient psychiatric population.

BACKGROUND: Information is sparse concerning migraine distribution in mood disorder subjects based mainly on psychiatric disorder. METHODS: In a sample of 283 normothymic mood disorder outpatients on maintenance treatment with serotonin reuptake inhibitors (SSRIs) or lithium, we investigated migraine distribution and clinical variables possibly related to comorbidity risk between mood disorder and migraine. RESULTS: Some 26.8% of the sample met criteria for migraine with migraine age of onset earlier than mood disorder age of onset; familiarity for mood disorder and migraine was strictly related to comorbidity risk in probands. Long-term treatment with lithium salts subjectively improved migraine outcome. CONCLUSIONS: These results could support the bidirectional association between the two clinical forms, considering the familial and pharmacological patterns.

Further evidence of a combined effect of SERTPR and TPH on SSRIs response in mood disorders.

We reported an independent association of the short variant of the serotonin transporter gene-linked polymorphic region (SERTPR) and tryptophan hydroxylase (TPH) genes with antidepressant response to selective serotonin reuptake inhibitors (SSRIs). The aim of the present study was to confirm the effect of the SERTPR and TPH gene variants on the SSRIs antidepressant activity in a new sample of major and bipolar depressives. Two hundred and twenty one inpatients (major depressives = 128, bipolar disorder = 93) were treated with SSRIs (fluvoxamine or paroxetine) for 6 weeks; the severity of depressive symptoms was weekly assessed with the Hamilton Rating Scale for Depression (HAMD). SERTPR and TPH variants were determined using PCR-based techniques, 220 subjects genotyped for SERTPR and 221 for TPH that were never included in previous studies. SERTPR*s/s variant association with a poor response to SSRI treatment was confirmed, even if with less significant P values (P = 0.034), independently from clinical variables; pooling the present sample with previous ones we observed a highly significant effect (P < 0.000001). TPH*A/A variants showed higher HAMD scores throughout the trial but with only a trend in the same direction of our previous study in terms of a worse response of A/A genotypes. Thus, the previous positive association was not fully replicated for TPH. The present independent replication confirms SERTPR variants as a liability factor for antidepressant efficacy while the TPH effect is not unequivocal.