Bupropion SSRIs

If depression is a problem, many clinicians prefer an antidepressant as an augmentation strategy. Because of the problems mentioned earlier, most now avoid using TCAs to treat ADHD. Bupropion, SSRIs, and venlafaxine are viable alternatives, and may add to the effect of the stimulant. Bupropion and venlafaxine are believed to offer some additional improvement in attention. SSRIs may be more likely to improve impulsivity. Each should be started at a low dose and increased gradually. None of these are approved for use in children however. 

In adults, mood stabilizers reduce the risk of cycling and have modest antidepressant effects (APA, 1994b). For patients with bipolar depression who do not respond to mood stabilizers alone, an antidepressant should be added to the treatment. It appears that bipolar depressed patients may be less likely to respond to TCAs than patients with unipolar depressions, who may show a more favorable response to bupropion, SSRI, or MAOIs. Furthermore, some studies, but not all, have also suggested that bupropion and the MAOIs are less likely to produce mania and less rapid cycling (APA, 1994b Compton and Nemeroff, 2000). 

Although more stimulating antidepressants (e.g., bupropion, SSRIs, venlafaxine, or certain MAOIs) do not potentiate alcohol, they can produce insomnia. To minimize this problem, the dose may be given earlier in the day. TCAs may cause episodes of excitement (rare), confusion, or mania, usually in patients with an underlying psychotic illness, suggesting that a preexisting disorder must be present for these drugs to exert any psychotomimetic effects. 

The starting dose is the usual therapeutic dose for most of the SSRIs, duloxetine, and mirtazapine, whereas there is usually need for at least some upward titration of venlafaxine, bupropion,... 

Optimize the dose of mood stabilizing medication(s) before adding on lithium, lamotrigine, or antidepressant (e.g., bupropion or an SSRI) if psychotic features are present, add on an antipsychotic ECT used for severe or treatment-resistant depressive episodes or for psychosis or catatonia... 

Switching non-responsive patients from an SSRI to an SNRI led 25 per cent of them to get better. Change from an SSRI to bupropion produced virtually the same remission rate (26 per cent). But what of the patients who were not switched to a different class of antidepressant, but instead were simply given another SSRI Twenty-seven per cent of these patients also got better - a remission rate that is virtually identical to that produced by changing to a different type of medication. In other words, the rate of improvement did not depend on the kind of drug to which the patient had been switched. Simply changing from one SSRI to another was as effective as changing to a completely... 

Stewart, Andrew A. Nierenberg, Michael E. Thase, Louise Ritz, Melanie M. Biggs, Diane Warden, James F. Luther, Kathy Shores-Wilson, George Niederehe and Maurizio Fava, Bupropion-Sr, Sertraline, or Venlafaxine-Xr after Failure of SSRIs for Depression , New England Journal of Medicine 354 (2006b) 1231-42... 

Drug therapies include tricyclic antidepressants and SSRIs. Treatment should be continued for at least 29 weeks. Nortriptyline, amitriptyline, clomipramine, desipramine, fluvoxamine, and bupropion have been used successfully. 

After more than a decade of use, bupropion (24) is considered a safe and effective antidepressant, suitable for use as first-line treatment. In addition, it is approved for smoking cessation and seasonal affective disorder. It is also prescribed off-label to treat the sexual dysfunction induced by SSRIs. Bupropion is often referred to as an atypical antidepressant and has much lower affinity for the monoamine transporters compared with other monoamine reuptake inhibitors. The mechanism of action of bupropion is still uncertain but may be related to inhibition of dopamine and norepinephrine reuptake transporters as a result of active metabolites [71,72]. In a recently reported clinical trial, bupropion extended release (XL) had a sexual tolerability profile significantly better than that of escitalopram with similar re-... 

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]. 

Tricyclic drugs have, as the name implies, a three-ring structure, and interfere with reuptake of norepinephrine and/or serotonin into axon terminals. Tricyclic drugs include imipramine (Tofranil), amitriptyline (Elavil), clomipramine (Anafranil), and nortriptyline (Pamelor, Aventil). Tricyclics have the occasional but unfortunate cardiovascular side effects of arrhythmia and postural hypotension. Newer, nontricyclic antidepressants have been developed that are collectively referred to as SSRIs. These have a potent and selective action on serotonin, and lack the cardiovascular side effects of the tricyclics. These include fluoxetine (Prozac), paroxetine (Paxil), sertraline (Zoloft), and fluvoxamine (Luvox). A fifth SSRI, citalopram (Celexa) has been used in Europe and has recently been approved in the United States. Venlafaxine (Effexor) blocks reuptake of norepinephrine and serotonin, while bupropion (Wellbutrin) acts on both dopamine and norepinephrine. 

Sexual function One of the potential benefits of hypericum is the apparent reduced or lack of adverse effects upon sexual function, compared to pharmaceutical antidepressants. The SSRIs are particularly notorious for inhibition of sexual function, whereas antidepressants with dopaminergic actions (e.g., bupropion) do not, and may actually enhance sexual function (Rosen et al. 1999 Piazza et al. 1997). Anecdotal reports and the fact that there are no clinical reports of sexual dysfunction with hypericum is encouraging, but it remains to be tested empirically. 

Atypical Antidepressants. The atypical antidepressants are not a true class in the same sense as SSRIs or TCAs. There is no unifying property to these antidepressants. Each of these antidepressants is actually a class unto itself that is structurally and functionally different from all other antidepressants. The atypical antidepressants include trazodone (Desyrel), bupropion (Wellbutrin), venlafaxine (Effexor), duloxetine (Cymbalta), nefazodone (Serzone), and mirtazapine (Remeron). 

Ischemic heart disease SSRIs Bupropion MAOIs... 

Dementia SSRIs Bupropion Duloxetine Mirtazapine Nefazodone Trazodone Venlafaxine TCAs... 

If the depressive symptoms do not resolve when treatment with one of the aforementioned mood stabilizers has been maximized, adjunctive therapy with an antidepressant or second mood stabilizer should be considered. SSRIs and bupropion are well tolerated by bipolar patients and appear to hold less potential to induce mania than TCAs. Nevertheless, treatment with any antidepressant should not be started until it has been confirmed that the patient s mood stabilizer is at a therapeutic level. If treatment with two or more of these first-line antidepressants is unsuccessful, a MAOI should be considered. 

Depression SSRIs SNRIs Mirtazapine Bupropion Nortriptyline Desipramine ... 

Currently, the antidepressants of choice are the SSRIs because they have been shown to be efficacious and safe for the treatment of children and adolescents with MDD, but further research on the other new antidepressants (e.g., bupropion, venlafaxine, nefazodone, mirtazapine) is needed. Patients should be treated with adequate doses for at least 6 weeks before declaring lack of response to treatment (treatment of nonresponders is described below) (AACAP, 1998 Hughes et ah, 1999 Fig. 36.1). 

MDD (Birmaher et al., 1996b Keller et al., 2001), and in adults they appear to be poor antidepressants for patients with bipolar depression or may induce rapid cycling (APA, 1994b, 2000), it remains to be seen whether the combination of mood stabilizers and other antidepressants such as bupropion and SSRIs will yield more complete prophylaxis. 

Case reports have suggested that adding stimulant medications or combining a SSRI and a TCA or bupropion may also be effective (APA, 2000), but these combinations need to be done with caution, given the possibility of drug interactions (e.g., SSRIs cytochrome inhibition leading to toxic TCA levels). Additionally, in adults, the combination of antidepressants and psychotherapy (CBT, IPT) for patients with severe or treatment-resistant depression has been found useful (APA, 2000 Keller et al., 2000). 

According to the Expert Consensus Panel for Mental Retardation Rush and Frances, (2000), the mainstays of the pharmacological treatment of acute mania or bipolar disorder in adults are anticonvulsant medications (divalproex, valproic acid, or carbamazepine) or lithium. Both divalproex or valproic acid and lithium were preferred treatments for classic, euphoric manic episodes. Divalproex or valproic acid was preferred over lithium and carbamazepine for mixed or dysphoric manic episodes and rapid-cycling mania. For depressive episodes associated with bipolar disorder, the addition of an antidepressant (SSRI, bupropion, or venlafaxine) was recommended. According to the Expert Consensus Panel, the presence of MR does not affect the choice of medication for these psychiatric disorders in adults. 

In the Expert Consensus survey, the use of the SSRIs was endorsed as the first-line treatment for a major depressive episode (Rush and Frances, 2000). The SSRIs were followed, at some distance, by venlafaxine, nefazodone, bupropion, and tricyclics, in that order. The warning against using bupropion in the presence of epilepsy constitutes a limitation on its use in the developmental disabilities. Clearly, more research is needed on the effects of antidepressants in both children and adolescents with MR and depression, as there are only four studies available thus far and that did not focus on age. 

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