The use of mood stabilizers is well documented in unipolar and bipolar patients (especially lithium in TCAs nonresponders), and two

modalities of response have been described: one group responds during the first week, while the second responds after a delay of 4 to 6 weeks (for review see ref 133). The dose of lithium used in this strategy (ie, 450 to 600 mg/day) is generally lower than that used for the treatment of acute Inhibitors,research,lifescience,medical mania or prophylaxis of bipolar disorder. Similarly, plasma lithium levels are lower in the range of 0.4 to 0.8 mEq/L. However the risks associated with lithium augmentation compared with that of switching antidepressant drugs needs to be weighted. Concerning the Inhibitors,research,lifescience,medical antiepileptic drugs (such as carbamazepine/oxcarbazepine, valproate, lamotrigine) their efficacy as adjuvant therapy has been demonstrated in bipolar patients (especially in rapid-cyclers). Thyroid hormones are useful in euthyroid patients for converting nonresponders into responders. It has been assumed that tri-iodothyronine (T3) would be preferentially indicated in unipolar patients (a 25-μg to 37.5-μg daily dose accelerates the time Inhibitors,research,lifescience,medical of response to antidepressants), while thyroxine (T4) combined with lithium would be useful in the prevention of mood episodes in bipolar patients (however the daily dose is generally high, about 200 to 400 μg, and

this may lead to possible adverse effects [thyrotoxicosis]). Dopamine agonists such as bromocriptine, pergolide, pramipexole, and ropinirole have been used with promising results as adjuvant to antidepressants especially in bipolar patients.134 These agonists are also useful in depressed patients with Parkinson’s disease and in patients with restless Inhibitors,research,lifescience,medical legs syndrome. Atypical antipsychotics such

as risperidone,135 olanzapine,136 and aripiprazole137 may also be useful as adjunctive medication in nonpsychotic treatment-resistant patients. Psychostimulants such as d-amphetamine, methylphenidate, Inhibitors,research,lifescience,medical and modafinil added to antidepressants have also been found to be effective in resistant depression.138,139 Electroconvulsive therapy (ECT) remains an option for resistant BKM120 ic50 depression, Fossariinae although there is only a weak possibility that a given patient will respond to ECT if he or she has previously failed to respond to pharmacotherapy140 Transcranial magnetic stimulation (which involves the depolarization of neurons in a localized area of the brain by applying a powerful magnetic field in rapid flux), vagus nerve stimulation, and deep brain stimulation have been proposed as alternatives to ECT.141 The efficacy of these approaches is promising, but needs further confirmation. Chronotherapeutics such as wake therapy- single or repeated sleep deprivation, total (all night) or partial (second half of the night) – and light therapy have been proposed as adjuvant to conventional antidepressants in unipolar patients, or lithium in bipolar patients (for review see ref 142).

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