Bupropion refractory

Triple reuptake inhibitors (TRIs), which inhibit reuptake at all three transporters, have attracted considerable interest in recent years [77]. The involvement of dopamine reuptake in the etiology of depression and other CNS disorders has been recognized [29,30]. As a result, TRIs have been proposed to offer a faster onset of action and improved efficacy for depression over currently prescribed single or dual action monoamine reuptake inhibitors. Historically, the mesocorticolimbic dopamine pathway is thought to mediate the anhedonia and lack of motivation observed in depressed patients [78,79]. In addition, methylphenidate, both immediate release and extended release formula, has been found to be effective as an augmenting agent in treatment-resistant depression [4]. Furthermore, clinical studies using the combination of bupropion and an SSRI or SNRI have showed improved efficacy for the treatment of MDD in patients refractory to the treatment with SSRIs, SNRIs, or bupropion alone [5,80,81]. 

Dassa D, Kaladjian A, Azorin JM, et al Clozapine in the treatment of psychotic refractory depression. Br J Psychiatry 163 822-824, 1993 Dauge V, Steimes P, Derrien M, et al CCK8 effects on motivational and emotional states of rats involve CCKA receptors of the postero-median part of the nucleus accumbens. Pharmacol Biochem Behav 34 157-163, 1989 Davidson J Seizures and bupropion a review. J Clin Psychiatry 50 256-261, 1989 Davidson J, Pelton S Eorms of atypical depression and their response to antidepressant drugs. Psychiatry Res 17 87-95, 1986 Davidson JR, Miller R, Turnbull CD, et al Atypical depression. Arch Gen Psychiatry 39 527-534, 1982... 

The combination of bupropion with an M AOI is potentially dangerous, but less so than the combination of serotonergic drugs and MAOIs. Although the practice is not recommended, MAOIs and bupropion have been combined in patients with refractory depression. 

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),... 

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