Treatment of bipolar disorder: a complex treatment for a multi-faceted disorder

Background: Manic-depression or bipolar disorder (BD) is a multi-faceted illness with an inevitably complex treatment. Methods: This article summarizes the current status of our knowledge and practice of its treatment. Results: It is widely accepted that lithium is moderately useful during all phases of bipolar illness and it might possess a specific effectiveness on suicidal prevention. Both first and second generation antipsychotics are widely used and the FDA has approved olanzapine, risperidone, quetiapine, ziprasidone and aripiprazole for the treatment of acute mania. These could also be useful in the treatment of bipolar depression, but only limited data exists so far to support the use of quetiapine monotherapy or the olanzapine-fluoxetine combination. Some, but not all, anticonvulsants possess a broad spectrum of effectiveness, including mixed dysphoric and rapid-cycling forms. Lamotrigine may be effective in the treatment of depression but not mania. Antidepressant use is controversial. Guidelines suggest their cautious use in combination with an antimanic agent, because they are supposed to induce switching to mania or hypomania, mixed episodes and rapid cycling. Conclusion: The first-line psychosocial intervention in BD is psychoeducation, followed by cognitive-behavioral therapy. Other treatment options include Electroconvulsive therapy and transcranial magnetic stimulation. There is a gap between the evidence base, which comes mostly from monotherapy trials, and clinical practice, where complex treatment regimens are the rule

Depressão resistente a tratamento: uma revisão das estratégias farmacológicas de potencialização de antidepressivos Treatment-resistant depression: review of pharmacologic antidepressant strategies

OBJETIVO: Fazer uma revisão sobre oito estratégias farmacológicas de potencialização de antidepressivos na DRT. MÉTODOS: Fez-se um levantamento bibliográfico de 1990 até janeiro de 2006, nas bases eletrônicas de busca Medline, LILACS e da Biblioteca Cochrane, utilizando-se os termos de busca treatment, resistant, refractory e depression e os descritores depression, drug resistance e augmentation, incluindo apenas ensaios controlados duplo-cegos. Foi consultada a referência dos artigos para obtenção de ensaios realizados em data anterior a 1990 e artigos originais de valor histórico. RESULTADOS: Foram encontrados 17 estudos duplo-cegos com o lítio, seis com o hormônio tireoidiano, dois com a buspirona, seis com o pindolol, um com a carbamazepina, dois com a lamotrigina e quatro com a olanzapina. Foram favoráveis à potencialização 41,2% dos ensaios com lítio; 60% daqueles com hormônio tireoidiano e antidepressivos tricíclicos e nenhum com hormônio tireoidiano e inibidores seletivos da recaptação da serotonina (ISRS); 50% dos com pindolol; 100% dos ensaios com carbamazepina e 40% daqueles com olanzapina. Nenhum dos estudos com a buspirona foi favorável. No único estudo com lamotrigina não houve eficácia de tratamento na avaliação pelo critério principal, mas superioridade ao placebo em critérios secundários. CONCLUSÃO: Na DRT há evidência de eficácia apenas em relação ao lítio na potencialização de várias classes de antidepressivos e ao hormônio tireoidiano na potencialização de tricíclicos. A olanzapina foi razoavelmente estudada e sua eficácia não foi estabelecida. Os poucos estudos realizados com a buspirona e o pindolol não comprovaram sua eficácia. A carbamazepina foi muito pouco estudada, e a lamotrigina ainda não foi adequadamente avaliada.<br>OBJECTIVE: The aim of this study is to review eight pharmacologic antidepressant augmentation strategies in TRD. METHODS: Database search on Medline, LILACS and Cochrane Library, from 1990 to June 2006 using the words treatment, resistant, refractory, depression and the medical subject headings depression, drug resistance and augmentation. Double-blind controlled trials and reviews were included. We also consulted reference of the articles in order to obtain studies and original articles of historical value from before 1990. RESULTS: There were 17 double-blind trials with lithium, six with thyroid hormone, two with buspirone, six with pindolol one with carbamazepine, two with lamotrigine and four with olanzapine. Forty-one percent of the trials with lithium, 60% of those with thyroid hormone and tricyclics, 0% of the ones with thyroid hormone and selective serotonin reuptake inhibitors (SSRI), 50% of those with pindolol, 100% of those with carbamazepine and 40% of the ones with olanzapine were favorable. No trials with buspirone were favorable. The only trial with lamotrigine did not show efficacy using the main outcome measures. Otherwise, there was superiority over placebo on secondary measures. CONCLUSION: Only lithium and thyroid hormone showed efficacy as antidepressant augmentation strategies for TRD. Olanzapine was reasonably studied and did not prove its efficacy. There were just a few studies on buspirone and pindolol and they were not favorable to them. Carbamazepine was studied very little. Lamotrigine was not adequately evaluated

Striatal Dopamine D-2/3 Receptor Availability in Treatment Resistant Depression

Several studies demonstrated improvement of depressive symptoms in treatment resistant depression (TRD) after administering dopamine agonists which suggest abnormal dopaminergic neurotransmission in TRD. However, the role of dopaminergic signaling through measurement of striatal dopamine D-2/3 receptor (D2/3R) binding has not been investigated in TRD subjects. We used [I-123] IBZM single photon emission computed tomography (SPECT) to investigate striatal D2/3R binding in TRD. We included 6 severe TRD patients, 11 severe TRD patients on antipsychotics (TRD AP group) and 15 matched healthy controls. Results showed no significant difference (p = 0.75) in striatal D2/3R availability was found between TRD patients and healthy controls. In the TRD AP group D2/3R availability was significantly decreased (reflecting occupancy of D2/3Rs by antipsychotics) relative to TRD patients and healthy controls (p <0.001) but there were no differences in clinical symptoms between TRD AP and TRD patients. This preliminary study therefore does not provide evidence for large differences in D2/3 availability in severe TRD patients and suggests this TRD subgroup is not characterized by altered dopaminergic transmission. Atypical antipsychotics appear to have no clinical benefit in severe TRD patients who remain depressed, despite their strong occupancy of D2/3Rs