Refractory unipolar depression

Lee W, Cleare A. Lithium augmentation in treatment-refractory unipolar depression. Br J Psychiatry 2003 182 456-7. 

Mood stabilisers are used to regulate the cyclical change in mood characteristic of bipolar disorder, since they can attenuate both manic and depressive phases. Their main use is as a prophylactic for manic depression and unipolar mania. However, they can also be administered concomitantly with antidepressants for refractory (non-responsive) unipolar depression. 

Hypothyroidism can precipitate a depression and be a risk factor for rapid cycling thyroid supplementation can be used for refractory rapid cycling and augmentation of antidepressants in unipolar depression. 

Charney DS, Nelson JC Delusional and nondelusional unipolar depression further evidence for distinct subtypes. Am J Psychiatry 138 328-333, 1981 Charney DS, Menekes DB, Heninger GR Receptor sensitivity and the mechanism of action of antidepressant treatment. Arch Gen Psychiatry 38 1160-1180, 1981 Charney DS, Price LH, Heninger GR Desipramine-yohimbine combination treatment for refractory depression. Arch Gen Psychiatry 43 1155-1161, 1986 Charney DS, Goodman WK, Price LH, et al Serotonin function in OGD a comparison of the effects of tryptophan and mGPP in patients and healthy subjects. Arch Gen Psychiatry 45 177-185, 1988... 

Poitou P, Bohuon C Catecholamine metabolism in the rat brain after short and long term hthium administration. J Neurochem 25 535-537, 1975 Pollack MH, Hammerness P Adjunctive yohimbine for treatment of refractory depression. Biol Psychiatry 33 220-221, 1993 Pollack MH, Rosenbaum JF Verapamil in the treatment of recurrent unipolar depression. Biol Psychiatry 22 779-782, 1987... 

Lithium has been proven effective for acute and prophylactic treatment of both manic and depressive episodes in patients with bipolar illness (American Psychiatric Association 2002). However, patients with rapid-cycling bipolar disorder (i.e., patients who experience four or more mood disorder episodes per year) have been reported to respond less well to lithium treatment (Dunner and Fieve 1974 Prien et al. 1984 Wehr et al. 1988). Lithium is also effective in preventing future depressive episodes in patients with recurrent unipolar depressive disorder (American Psychiatric Association 2002) and as an adjunct to antidepressant therapy in depressed patients whose illness is partially refractory to treatment with antidepressants alone (discussed in Chapter 2). Furthermore, hthium may be useful in maintaining remission of depressive disorders after electroconvulsive therapy (Coppen et al. 1981 Sackeim et al. 2001). Lithium also has been used effectively in some cases of aggression and behavioral dyscontrol. 

Although the efficacy of tricyclic antidepressants in the treatment of unipolar depression is beyond reproach, the side-effect profile of these agents makes them less desirable as first-line therapeutic agents. Introduction of selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine, paroxetine, sertraline, citalopram and fluvoxamine in the past decade has revolutionized the treatment of depression universally. The side-effect profile of SSRIs, such as nausea, diarrhea and sexual dysfunction, is considerably more benign than that of tricyclic drugs. Multiple controlled trials have proven the efficacy of SSRIs vs. placebo (Nemeroff, 1994). Recently, a number of SNRIs (serotonin and noradrenaline reuptake inhibitors) and so-called atypical antidepressants have been marketed that may have additional advantages over SSRIs, such as more rapid onset of action (venlafaxine. mirtazapine) and low sexual side-effect potential ( bupropion, nefazodone). Additionally, it appears that venlafaxine may be more efficacious in cases of treatment-refractory depression (Clerc et al., 1994 Fatemi et al., 1999). Finally, in a recent report (Thase et al., 2001),... 

Lara DR, Bisol LW, Munari LR. Antidepressant, mood stabilizing and procognitive effects of very low dose sublingual ketamine in refractory unipolar and bipolar depression. Int J Neuropsychopharmacol/Off Sci J CoU Int Neuropsychopharmacol 2013 16 2111-7. 

Joffe RT, Singer W, Levitt AJ, et al A placebo-controlled comparison of lithium and triiodothyronine augmentation of tricyclic antidepressants in unipolar refractory depression. Arch Gen Psychiatry 50 387-393, 1993... 

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