Venlafaxine Bupropion

Bupropion Venlafaxine Duloxetine Trazodone Nefazodone Mirtazapine... 

Like bupropion, venlafaxine comes in immediate-release and extended-release preparations. The immediate-release form is taken twice a day starting at 37.5 to 75 mg/day and increased to 75 mg/day after 1 week. The effective dose range is 75-375mg/day. The extended release form is started once daily at 37.5mg/day and is also effective at 75-375 mg/day. The effective dose range is similar to the immediate-release form. 

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). 

Other alternatives to the stimulants that have been studied for treatment of ADHD in children and adults include the tricyclic antidepressants desipramine and nortriptyline the newer antidepressants bupropion, venlafaxine, and atomoxetine the beta-blocker pindolol and the selective monoamine oxidase inhibitor, deprenyl. Across these agents, the number of controlled studies varies from none (nortriptyline) to four (bupropion). Only deprenyl and desipramine have been studied in children with ADHD and tic disorders. 

Medications play an important part in the treatment of ADD. Stimulants are the mainstay of the treatment of ADD methylphenidate (Ritalin), dextroamphetamine (Dexedrine), and pemoline (Cylert). These differ in their half-lives, with Ritalin having the shortest and Cylert the longest. A warning has recently been issued about Cylert because of reports of sometimes fatal liver toxicity. Thus, it is recommended that it be used only if methylphenidate and dextroamphetamine are ineffective. There is individual variability in resporise, so that a person who does not respond to one may respond well to another. Other medications can also be effective in the treatment of ADD and may be useful, especially in residual ADD, where substance abuse may be an issue. These include tricyclic antidepressants (especially desipramine and imi-pramine) SSRIs, bupropion, venlafaxine, and clonidine. There are reports of antipsy-chotics and lithium being helpful in selected cases, as well. 

High suicide risk Less toxic antidepressants (fluoxetine, trazodone, paroxetine, sertraline, bupropion, venlafaxine, nefazodone)... 

Retarded or anergic SSRI, bupropion, venlafaxine, secondary amine TCA... 

Severe, recurrent depression Combined SSRI + TCA or bupropion venlafaxine TCAs or bupropion alone... 

Antidepressants Desipramine, imipramine, sertraline, fluoxetine, paroxetine, venlafaxine, bupropion, nefazodone, mirtazapine, gepirone, amineptine Mixed findings suggest that better designed studies may find a niche for some of these drugs. Amineptine was effective for withdrawal symptoms. 

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,... 

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... 

Bupropion and venlafaxine may also be chosen because of their milder anticholinergic and less frequent cardiovascular side effects. 

The STAR D study showed that one in three depressed patients who previously did not achieve remission with an antidepressant became symptom-free with the help of an additional medication (e.g., bupropion sustained release), and one in four achieved remission after switching to a different antidepressant (e.g., venlafaxine XR). 

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. 

Atypical antidepressants Bupropion Duloxetine Mianserin Mirtazapine Nefazodone Reboxetine Trazodone Venlafaxine... 

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). 

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

Nortriptyline (Pamelor). A recent study suggested that the tricyclic antidepressant nortriptyline, like bupropion, is effective in the treatment of smoking cessation. Nortriptyline does not have any significant effect on dopamine reuptake activity, but it does increase norepinephrine availability. Like bupropion, nortriptyline may therefore reduce the physical symptoms of nicotine withdrawal. Because nortriptyline carries the danger of lethality in overdose and has the unfavorable side effect profile of the tricyclics, we do not recommend its use for smoking cessation. However, it does raise the question as to whether other newer antidepressants that increase norepinephrine activity (e.g., venlafaxine, mirtazapine, duloxetine) may also prove to be effective treatments for nicotine withdrawal. 

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. 

The so-called atypical antidepressants such as venlafaxine and bupropion can be tried, but their safety and efficacy in treating patients with dementia have not been well studied. The older tricyclic antidepressants and monoamine oxidase inhibitors are not tolerated well by demented patients and should be avoided. Two possible exceptions are nortriptyline (Pamelor) and desipramine (Norpramin), but even these should be tried only after the newer antidepressants have proved ineffective. 

Figure 7.3. Structural formulae of the noradrenaline (norepinephrine)/dopamine reuptake inhibitor amfebutamone (bupropion) and some nonselective noradrenaline and serotonin (5-hydroxytr3 tamine 5-HT) reuptake inhibitors (venlafaxine, and...

D. Mirtazapine acts at serotonin and adrenergic receptors and does not effect reuptake of neurotransmitters. Venlafaxine is a mixed serotonin-norepinephrine reuptake inhibitor. Bupropion inhibits norepinephrine and dopamine reuptake. 

E. Nefazodone,fluoxetine,mirtazapine, and venlafaxine have minimal effects on seizure threshold. Bupropion in its original formulation caused seizures in 4 in 1000 patients. Although this has been reduced with the slow release form of the medication (Wellbutrin SR), it remains a contraindication to prescribe this medication to patients with a history of seizures. 

C. Nortriptyline (Pamelor) is a TCA, and as a class these drugs require at least one steady-state blood level to safely and effectively use the medication. Paroxetine, venlafaxine, and bupropion have not had blood levels correlated to response, and their relatively low toxicity does not require therapeutic blood monitoring. Nardil is a MAOI, which can be... 

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. 

Newer antidepressants (such as the SSRIs, bupropion, and venlafaxine] probably achieved their impressive popularity primarily because their side-effect profiles were more favorable. Because dry mouth, blurry vision, tachycardia, lethargy, constipation, urinary hesitancy, and arrhythmias are deeply distressing to many, paucity of anticholinergic side effects from SSRIs was especially noteworthy. Convenience and simplicity of use are also favorable qualities for some newer agents. However, the decreased libido, anorgasmia, and erectile problems caused by SSRIs are of note and should be taken into consideration for long-term therapy. 

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),... 

Fatenri, S.H., Emamian, E.S., Kist, D. Venlafaxine and bupropion combination therapy in a case of treatment-resistant depression. Ann. Phannacother. 33, 701—703, 1999. 

Bupropion appears to be relatively free of adverse effects on sexual function, in contrast to the SSRIS or venlafaxine (168). 

In psychomotorically retarded patients, many clinicians prefer to use a less sedating drug (e.g., an SSRI, venlafaxine, bupropion, or desipramine), but definitive evidence is lacking. 

Those who fail to respond to an SSRI may respond to a TCA, and vice versa. Thus, these two broad-spectrum classes can be used in a sequential strategy to adequately treat the majority of cases. However, many physicians try another newer antidepressant (e.g, venlafaxine, bupropion, nefazodone) in such patients because of the safety and tolerability problems associated with TCAs. Of note, the tolerability profile of secondary amine TCAs such as desipramine is as favorable as any of the newer antidepressants and probably better than nefazodone. Nevertheless, the secondary amine TCAs have a therapeutic index as narrow as tertiary amine TCAs (e.g., amitriptyline, imipramine) in terms of lethality in overdoses resulting from cardiotoxicity. 

No comparable long-term studies have been done with the SSRIs, bupropion, nefazodone, venlafaxine, or mirtazapine. 

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. 

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