O advento de medicamentos antidepressivos tornou a depressão um problema médico, passível de tratamento. Nas últimas cinco décadas, a psicofarmacologia da depressão evoluiu muito e rapidamente. Os primeiros antidepressivos - os antidepressivos tricíclicos (ADTs) e os inibidores da monaminooxidase (IMAOs) - foram descobertos através da observação clínica. Os ADTs apresentavam boa eficácia devido à sua ação, aumentando a disponibilidade de norepinefrina e serotonina. Seu uso foi limitado em função do bloqueio de receptores de histamina, colinérgicos e alfa-adrenérgicos que acarretavam efeitos colaterais levando à baixa tolerabilidade e risco de toxicidade. Da mesma forma, o uso dos IMAOs ficava comprometido em função do risco da interação com tiramina e o risco de crises hipertensivas potencialmente fatais. A nova geração de antidepressivos é constituída por medicamentos que agem em um único neurotransmissor (como os inibidores seletivos de recaptação de serotonina ou de noradrenalina) ou em múltiplos neurotransmissores/receptores, como venlafaxina, bupropion, trazodona, nefazodona e mirtazapina, sem ter como alvo outros sítios receptores cerebrais não relacionados com a depressão (tais como histamina e acetilcolina). Este artigo revisa a farmacologia dos antidepressivos, particularmente quanto ao mecanismo de ação, farmacocinética, efeitos colaterais e interações farmacológicas. Antidepressant drugs turned depression into a treatable medical problem. In the last five decades, the psychopharmacology of depression has evolved rapidly. Early antidepressants - tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs) - were discovered through clinical observation. The TCAs exhibited good antidepressant efficacy due to the enhancement in serotonin and norepinephrine availability. Its use was limited because of unwanted side effects and toxicity risk related to the blockade of histaminergic, cholinergic and alfa-adrenergic receptors. MAOIs can interact with tyramine to cause potentially lethal hypertension and present potentially dangerous interactions with various medications and over-the-counter drugs. The new generation of antidepressants includes the single-receptor selective serotonin or norepinephrine inhibitors and the multiple-receptor-acting antidepressants, such as venlafaxine, bupropion, trazodone, nefazodone, and mirtazapine. They do not act on other receptor sites not related to depression (such as histamine or acetilcholine). This paper reviews the pharmacology of antidepressants, including its mechanism of action, pharmacokinetics, side effects and drug-drug interactions
Pharmacotherapies for BD should be chosen to minimize neurocognitive side-effects, which may already be compromised by the disease process itself. Neurocognitive evaluation should be considered in BD patients to better evaluate treatment impact on neurocognition. A comprehensive neuropsychological evaluation also addressing potential variables and key aspects such as more severe cognitive deficits, comorbidities, differential diagnosis, and evaluation of multiple cognitive domains in longitudinal follow-up studies are warranted.
Bipolar disorder (BD) is a major public health problem characterized by progressive functional impairment. A number of clinical variables have been associated with progression of the disease, most notably number of affective episodes and presence of psychotic symptoms, both of which correlate with greater cognitive impairment, lower response rates for lithium, and possibly lower levels of neurotrophic factors. Oxidative damage to cytosine and guanosine (8-OHdG) has been described as a modulator of DNA methylation, but the extent of DNA oxidative damage involvement in BD remains unclear. The aim of this study was to evaluate the extent of DNA oxidative damage to 8-OHdG and 5-methylcytosine (5-HMec), as well as global methylation (5-Mec), in BD patients and healthy controls. Potential association with clinical variables was also investigated. DNA levels of 8-OHdG, 5-HMec and 5-Mec were measured in 50 BD type I patients and 50 healthy controls. DNA 8-OHdG levels were higher in BD patients compared to healthy controls and found to be positively influenced by number of previous manic episodes. BD subjects had lower levels of 5-HMec compared to controls, whereas this measure was not influenced by the clinical features of BD. Number of manic episodes was correlated with higher levels of 8-OHdG, but not of 5-Mec or 5-HMec. Lower demethylation activity (5-HMec) but no difference in global 5-Mec levels was observed in BD. This finding suggests that oxidative damage to 8-OHdG might be a potential marker of disease progression, although further prospective cross-sectional studies to confirm neuroprogression in BD are warranted.
OBJECTIVE: In this study, we aimed to quantify posture and body image in patients with major depressive disorder during episodes and after drug treatment, comparing the results with those obtained for healthy volunteers. METHOD: Over a 10-week period, we evaluated 34 individuals with depression and 37 healthy volunteers. Posture was assessed based on digital photos of the subjects; CorelDRAW software guidelines and body landmarks were employed. Body image was evaluated using the Body Shape Questionnaire. RESULTS: During depressive episodes (in comparison with the post-treatment period), patients showed increased head flexion (p < 0.001), increased thoracic kyphosis (p < 0.001), a trend toward left pelvic retroversion (p = 0.012) and abduction of the left scapula (p = 0.046). During remission, patient posture was similar to that of the controls. At week 1 (during the episode), there were significant differences between the patients and the controls in terms of head flexion (p < 0.001) and thoracic kyphosis (p < 0.001); at weeks 8-10 (after treatment), such differences were seen only for shoulder position. The mean score on the Body Shape Questionnaire was 90.03 during the depressive episode, compared with 75.82 during remission (p = 0.012) and 62.57 for the controls. CONCLUSION: During episodes of depression, individuals with major depressive disorder experience changes in posture and mild dissatisfaction with body image. The findings demonstrate that the negative impact of depression includes emotional and physical factors.
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