Desipramine efficacy

Trigclic Antidepressants. Imipramine (38) was introduced in the late 1950s as one of the first pharmacotherapies for depression. At that time, chlorproma2ine [50-53-3] was the first effective antipsychotic treatment to be discovered. Researchers looked for similar chemical stmctures and imipramine was found to be effective in the symptomatic treatment of depression. Over the years, other congeners, such as desipramine (39), amitriptyline (40), and dothiepin (41), were synthesized and shown to be clinically efficacious antidepressant dmgs (121). These substances, known under the general mbric of tricycHc antidepressants, share a basic chemical stmcture comprising... 

A meta-analysis of placebo-controlled studies by Levin and Lehman (1991) showed that desipramine produced greater cocaine abstinence than placebo. Although a more recent review did not concur (Lima et al. 2001), secondary analyses of studies with imipramine, desipramine, and bupropion suggested that depressed cocaine abusers are more likely to show significant reductions in cocaine abuse than nondepressed cocaine abusers (Margolin et al. 1995 Nunes et al. 1991 Ziedonis and Kosten 1991). Furthermore, recent work with desipramine supported its efficacy in opioid-dependent patients, particularly in combination with contingency management therapies (Kosten et al. 2004 Oliveto et al. 1999). 

Desipramine and sertraline are efficacious for MS-related depression.15 If beta interferon treatment appears to be causing depression, discontinuation could be considered. 

Treatment with imipramine, the most studied TCA, leaves 45% to 70% of patients panic free. Both desipramine and clomipramine have demonstrated effectiveness in PD as well. Despite their efficacy, TCAs are considered second- or third-line pharmacotherapy due to poorer tolerability and toxicity on overdose.48,49 TCAs are associated with a greater rate of discontinuation from treatment than SSRIs.53 PD patients taking TCAs may experience anticholinergic effects, orthostatic hypotension, sweating, sleep disturbances, dizziness, fatigue, sexual dysfunction, and weight gain. Stimulant-like side effects occur in up to 40% of patients.49... 

Additional ADRs linked to diet pills include psychosis myocardial ischemia drug interactions, such as the interaction of fenfluramine with imipramine, fenfluramine with amitriptyline or desipramine, or the toxic reaction between fluoxetine and phentermine and the release of serotonin while inhibiting its reuptake, contributing to hyperserotonin reactions. When the next craze takes hold of patients and their physicians, hopefully physicians and pharmacists will take a more vocal position and recommend restraint, xmtil some proof of efficacy and lack of toxicity is shown for new faddish off-label combinations. 

Antidepressants. In the early 1980s, the recognition that depression is a frequent comorbid feature of BN coupled with the observation that appetite changes are a common feature of depression led researchers to evaluate antidepressant treatment for BN. Since that time, a series of controlled studies have demonstrated efficacy for a wide assortment of antidepressants including the TCAs imipramine (Tofranil) and desipramine (Norpramin), the MAOl phenelzine (Nardil), the SSRl fluoxetine (Prozac), and the atypical antidepressants trazodone (Desyrel) and bupropion (Wellbutrin). Overall, approximately two-thirds of antidepressant-treated patients with bulimia experience symptomatic improvement while nearly one-third achieves complete remission of binging and purging. In addition, the improvement in the symptoms of BN is not dependent on the presence of comorbid depression. 

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. 

Reboxetine is the only selective and reasonably potent noradrenaline reuptake inhibitor available clinically at the present time. Reboxetine has a chemical structure not dissimilar from viloxazine, an antidepressant which was of only limited clinical interest in the 1970s because of its weak efficacy and unacceptable side effects (nausea, vomiting and occasionally seizures). Unlike the secondary amine TCA antidepressants, such as maprotiline, desipramine, nortriptyline and protriptyline, reboxetine does not affect any other transporter or receptor system and therefore is largely devoid of TCA and SSRI-like side effects. In clinical trials, reboxetine has been shown to be as effective as the SSRIs in the... 

Children Not recommended for patients younger than 12 years of age. Safety and efficacy are not established for amoxapine in children younger than 16 years of age or trazodone or clomipramine in children younger than 10 years of age. The safety and efficacy of imipramine as temporary adjunctive therapy for nocturnal enuresis in pediatric patients younger than 6 years of age have not been established. The safety of the drug for long-term, chronic use as adjunctive therapy for nocturnal enuresis in pediatric patients 6 years of age and older has not been established. Safety and efficacy are not established in the pediatric age group for trimipramine, nortriptyline, protriptyline, and desipramine. 

Biederman, J., Baldessarini, R.J., Wright, V., Knee, D. and Harmatz, J. (1989) A double-blind placebo controlled study of desipramine in the treatment of attention deficit disorder I. Efficacy. J Am Acad Child Adolesc Psychiatry 28 777-784. 

Relapse prevention with medication has been studied in BN as well as AN. In 1991 Walsh et al. placed bulimics who had a 50% or more reduction in binge eating on desipramine in maintenance treatment. About half of the patients relapsed below the 50% reduction within 4 months, despite continued use of the medication. In a second multicenter collaborative study examining the efficacy of fluoxetine maintenance in bulimic patients who had responded to the drug with a 50% reduction of symptoms, the patients who were maintained on the active drug were significantly less likely to relapse than those who were switched to placebo at the end of the acute treatment phase (Romano, 1999). 

The only current evidence to support this view is the finding that the addition of desipramine to fluoxetine was better than desipramine alone in the treatment of patients with depression (J. C. Nelson et al. 1991). Desipramine alone resulted in the expected improvement of approximately 20% at week 1 and 40% at 2 weeks in 52 patients. In patients treated with the combination of fluoxetine and desipramine, the response was greatly accelerated, and a response of 42% was seen at the first week of treatment. At the end of 4 weeks of treatment, 71 % of the 14 patients on combined treatment were in complete remission compared with only 14% of those receiving desipramine alone. This study provides some evidence of the better efficacy seen with a double action on both noradrenaline and serotonin, but firm conclusions cannot be drawn because of the open nature of the investigation. 

Reboxetine is a pure noradrenaline reuptake inhibitor that is licensed as an antidepressant in the United Kingdom. Reboxetine has established efficacy based on placebo-controlled studies both in the short and the long term. Previous noradrenaline reuptake inhibitors, such as desipramine, nortriptyline, and maprotiline, have been relatively selective for noradrenaline compared... 

Barnes NM, Costall B, Naylor RJ, et al Normal densities of 5-HT3 receptor recognition sites in Alzheimer s disease. Neuroreport 1 253-254, 1990 Barnes R, Veith R, Okimoto J, et al Efficacy of antipsychotic medications in behaviorally disturbed dementia patients. Am J Psychiatry 139 1170-1174, 1982 Baron BM, Ogden AM, Siegel BW, et al Rapid down regulation of beta-adrenoceptors by co-administration of desipramine and fluoxetine. Eur J Pharmacol 154 25-134, 1988... 

Results of crossover studies indicate that lithium is efficacious in treating acute depression in bipolar subjects unequivocally (36%, 29/80) and partially (43%. 34/80). respectively (Xomberg and Pope, 1993 Keck and McElroy, 2002). Various antidepressants have shown variable rates of efficacy in the treatment of acute bipolar depression, i.e. desipramine (50%), maprotiline (67%), imipra-mine (40 60%), tranylcypromine (87%), moclobemide (53%) and fluoxetine (60%) (Keck and McElroy, 2002). Among the anticonvulsants, valproic add and lamotrigine appear to have some potential efficacy in the treatment of acute bipolar depression (Calabrese et al., 1992, 1999 Fatemi et al., 1997). 

Based on comparisons with imipramine and amitriptyline, desipramine and nortriptyline (secondary amine compounds) are comparable in efficacy with their tertiary amine parent compounds and clearly superior to placebo (Table 7-5). Clinically, they are often preferred to the tertiary amine compounds because of their less... 

Few data are available to guide this decision beyond clinical experience. There is a modest amount of evidence that nonresponders to TCAs, principally desipramine or imipramine, alone may respond to a SSRI alone and vice versa (136). No compelling evidence exists showing that nonresponders to one SSRI as a result of a lack of efficacy will respond to a second trial with another SSRI. There is limited confidence in the results of studies that have been done switching nonresponders from one SSRI to another for two reasons. First, virtually all have been open label and, second, most were conducted by the manufacturer of the second SSRI. Until there is more substantive evidence that switching from one SSRI to another is worthwhile, it may be more prudent to switch to a class of antidepressants with a different putative mechanism of action. 

Most efficacy trials with reboxetine have so far only been published in review articles ( 178). Most of these articles did not have peer review and do not contain the full details concerning methodology or results. This fact limits the ability to accurately determine its relative efficacy and tolerability. In short-term (4 to 8 weeks), placebo-controlled clinical trials, reboxetine produced a response (defined as at least a 50% reduction in severity scores) in 56% to 74% of patients. These results were statistically superior to placebo in most studies. Reboxetine was also found to be as effective as imipramine and desipramine in four double-blind, randomized, active-controlled (but not placebo-controlled) studies involving more than 800 outpatients or inpatients with major depression. Reboxetine produced equivalent antidepressant response rates compared with fluoxetine in two clinical trials, one of which was also placebo-controlled. However, reboxetine was reported to have improved social motivation and behavior more than fluoxetine as assessed by the newly developed Social Adaptation Self-Evaluation Scale. In all of the studies, reboxetine had a similar time (i.e., 2 to 3 weeks) to onset of the antidepressant efficacy as do other antidepressants. 

Remick RA, Fleming JAE, Buchanan RA, et al. A comparison of the safety and efficacy of alprazolam and desipramine in moderately severe depression. Can J Psychiatry 1985 30 597-601. 

Ban TA, Gaszner P, Aguglia E, et al. Clinical efficacy of reboxetine a comparative study with desipramine, with methodological considerations. Hum Psychopharmacoi 1998 13 S29-S39... 

In a double-blind comparison of lamotrigine versus desipramine or placebo, 450 unipolar depressed patients were studied. Lamotrigine was found to be significantly better than placebo, with desipramine falling between lamotrigine and placebo in terms of efficacy. 

A number of studies indicate that some but not all antidepressants are effective in ADHD. Spencer and colleagues (66) found 29 studies (involving 1,016 patients) that supported the efficacy of TCAs in the treatment of ADHD. Desipramine is the TCA with the most efficacy data. Desipramine, based on a meta-analysis of five randomized trials involving 170 ADHD patients had efficacy (i.e., effect size) comparable with that of methylphenidate ( 90, 91). However, desipramine produced a higher rate of adverse effects compared with psychostimulants. Moreover, several sudden, unexpected deaths have been reported in children on desipramine ( 92,... 

Although there are reasons to question whether desipramine had a role in these deaths, these reports have raised considerable concern among child and adolescent psychiatrists and have limited the use of this medication in this population. Some more limited evidence supports the efficacy of either imipramine or nortriptyline for ADHD (94, 95, 96 and 97). 

The first agent proven to be effective in OCD was the TCA, clomipramine. Its efficacy in pediatric-age patients with OCD was demonstrated in two double-blind, placebo-controlled studies (146, 147). These findings were further supported by a double-blind crossover study with desipramine ( 148). This latter study provided support for serotonin uptake inhibition being the mechanism of action responsible for the efficacy of clomipramine in OCD. Despite this evidence, there are several limitations to the use of clomipramine because of its multiple mechanisms of action ... 

By the 1990s antidepressants from the serotonin selective reuptake inhibitor (SSRI) class became recognized as preferred first-line treatments for anxiety disorder subtypes, ranging from obsessive-compulsive disorder, to panic disorder, and now to social phobia and posttraumatic stress disorder (Fig. 8—9). Not all antidepressants, however, are afficacious anxiolytics. For example, desipramine and bupropion seem to be of little help in several anxiety disorder subtypes. Documentation of efficacy... 

Tricyclic antidepressants. Imipramine and clomipramine have been the most extensively studied of the tricyclic antidepressants and both have demonstrated efficacy in treating panic disorder. Other tricyclic antidepressants that have shown some evidence of efficacy include desipramine, doxepin, amitriptyline, and nortriptyline. 

Desipramine is a tricyclic antidepressant that has been tested in several double-blind trials among cocaine addicts. Like cocaine, desipramine inhibits monoamine neurotransmitter reuptake, but its principal effects are on norepinephrine reuptake. It was hypothesized that desipramine could relieve some of the withdrawal symptoms of cocaine dependence and reduce the desire for cocaine during the vulnerable period following cessation of cocaine. This drug showed efficacy early in the epidemic in a group of patients who were primarily white collar intranasal cocaine users. The majority of subsequent studies of desipramine-using, more severely ill cocaine addicts have been negative. 

In healthy elderly patients, cautious use of a secondary amine TCA (desipramine or nortriptyline) may be appropriate because of their defined therapeutic plasma concentration ranges, well-established efficacy, and well-known adverse-effect profiles. 

Not recommended for first-line use in children with ADFID because of the availability of safer treatments with better documented efficacy and because of desipramine s potential for sudden death in children... 

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