Imipramine 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). 

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... 

In many clinical trials a positive control of a clinically established drug is often used for comparison purposes for example, a novel selective serotonin reuptake inhibitor (SSRI), may be compared with a more established tricyclic antidepressant, such as imipramine. The aim is to see whether the new SSRI is more efficacious or has fewer adverse side effects than the more established tricyclic (Chapter 12). In many such comparisons the new and older treatments are equally efficacious at relieving depression, but the newer drugs display fewer side effects this means that they are better tolerated by patients, so that they are more willing to continue taking the tablets. The high rates of compliance also mean that, in overall terms, newer drugs with fewer side effects tend to be more efficacious. 

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. 

Vorbach EU, Arnoldt KH, Hubner WD. (1997). Efficacy and tolerability of St. John s wort extract LI 160 versus imipramine in patients with severe depressive episodes according to ICD-10. Pharmacopsychiatry. 30(suppl 2) 81-85. 

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. 

Clinically used local anesthetics are either esters or amides. This structural element is unimportant for efficacy even drugs containing a methylene bridge, such as chlorpromazine (p. 236) or imipramine (p. 230), would exert a local anesthetic effect with appropriate application. Ester-type local anesthetics are subject to inactivation by tissue es-Ltillmann, Color Atlas of Pharmacology... 

As with imipramine, it is used for depression of various etiology. In terms of efficacy, it is analogous to imipramine. Surmontil is a synonym of trimipramine. 

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. 

This group includes compounds with actions on a range of neurotransmitter systems. Their antidepressant efficacy is mediated by reuptake inhibition of serotonin and noradrenaline, although side-effects such as sedation may also be useful. Their use in anxiety disorders is supported by a long history of clinical experience and a reasonable evidence base from controlled trials. Studies support the use of clomipramine (a potent serotonin reuptake inhibitor) in panic disorder and OCD (Lecrubier et al. 1997 Clomipramine Collaborative Study Group 1991), of imipramine in panic disorder and GAD (Cross-National Collaborative Panic Study 1992 Rickels et al. 1993), and of amitriptyline in PTSD (Davidson et al. 1993a). No controlled studies support the use of TCAs in social anxiety disorder. 

Boyer W (1995) Serotonin uptake inhibitors are superior to imipramine and alprazolam in alleviating panic attacks a meta-analysis. Int Clin Psychopharmacol 10 45-49 Brady K, Pearlstein T, Asnis GM, Baker D, Rothbaum B, Sikes CR, Farfel GM (2000) Efficacy and safety of sertraline treatment of posttraumatic stress disorder a randomized controlled trial. JAMA 283 1837-1844... 

A multicenter trial comparing more appropriate doses of imipramine (75 mg twice daily, N = 167) and St. John s wort extract (250 mg twice daily standardized to 0.2% hypericin, N = 157) showed no difference in efficacy after 6 weeks of treatment. However, St. John s wort seemed to reduce anxiety symptoms more often than imipramine and was better tolerated (Woelk, 2000). A study including 240 participants compared St. John s wort with fluoxetine in mild to moderate depression and also concluded that efficacy of both treatments was comparable (Schrader, 2000). These results have been replicated in a smaller trial us-... 

Although there are continuation and maintenance guidelines for the use of antidepressants for unipolar depression, it is not clear how long a patient with bipolar depression should be treated with these medications. Rates of recurrence of bipolar depression of approximately 60% have been observed in patients taking adequate doses of lithium, alone or in combination with imipramine (APA, 1994b). As the TCAs have not been shown to be efficacious for youth with... 

Sovner et al. (1998) have done an excellent job summarizing the data on antidepressants in patients with developmental disabilities. There have been nine reports of antidepressant use in adults with depression and MR and three reports of antidepressant use in children and adolescents. Eight of nine reports in adults were positive. The drugs studied included nialimide (n = 27), fluoxetine (9), imipramine (6), amoxapine (2), and nortriptyline (1) (total n = 45). In addition, Sovner et al. identified four reports of antidepressant use in children. One involved successful treatment with fluoxetine in an adolescent, another indicated efficacy with imipramine and amitriptyline in 9 of 12 children (Do-sen, 1982), and a third showed successful management in 3 of 4 children treated with imipramine or tryptophan plus nicotinamide (Dosen, 1990). One study of fluoxetine in depressed children with autism and MR witnessed improvement in depression but not in compulsive symptoms (Ghaziuddin and Tsai, 1991). 

Several preliminary lines of research have started to suggest that antidepressants, once considered ineffective in generalized anxiety disorder, may be very efficacious [Gorman and Kent 1999]. In particular, venlafaxine has been effective in treating generalized anxiety disorder in both open-label and double-blind trials, and imipramine and paroxetine were as effective as a benzodiazepine in the long-term treatment of generalized anxiety disorder. 

Some questions have been raised about the relative efficacy of the SSRls, particularly in severe depression. The pooled analyses of the data from blinded, controlled trials have tended to find similar levels of efficacy between the SSRls and the comparator TCA, imipramine. Paroxetine and fluvoxamine were both found in subanalyses of patients with severe depression included in large placebo- and imipramine-controlled studies to be more effective than imipramine in severe depression (S. A. Montgomery 1992a Ottevanger 1991 Tignol et al. 1992 Wakelin 1988]. However, imipramine may not be the TCA that is most effective in severe depression or may not have been used in the trials at an adequate dose. 

Efficacy. To date, more than 15 clinical trials have been conducted comparing fluvoxamine with other active agents and placebo. Imipramine was the most common comparator drug used, and studies have indicated that fluvoxamine was effective as the reference drug, although significantly supe-... 

Will medications known to sustain maintenance over several years continue to do so indefinitely Few studies have monitored antidepressant maintenance efficacy for periods exceeding several years (Prien and Kocsis 1995). Lacking data, the clinician can only hope that efficacy over several years will translate into sustained effectiveness over many years, decades, or indefinitely. This remains to be demonstrated. For imipramine, maintenance of euthymia has been systematically demonstrated in a small number of patients for at least 5 years (Kupfer 1992). Anecdotes suggest that SSRIs may lose some of their efficacy over time, but few convincing data support this to date. Considering the widespread use of SSRIs, research is sorely needed to address this question. 

Effective pharmacological treatment of panic disorder began with the antidepressant imipramine, but today a variety of efficacious agents are available for treating the symptoms of panic disorder. The four primary classes of... 

Katona CL, Hunter BN, Bray J A double-blind comparison of the efficacy and safety of paroxetine and imipramine in the treatment of depression with dementia. Int J Geriatr Psychiatry 13 100-108, 1998... 

Sheehan DV, Raj AB, Sheehan KH, et al The relative efficacy of buspirone, imipramine and placebo in panic disorder a preliminary report. Pharmacol Biochem Behav 29 815-817, 1988... 

It is thus understandable why some earlier authors previously doubted the efficacy of antidepressants in general (Weiner et al.. 1980) or the advantages of newer antidepressants compared with classical products (Song et al., 1993). However, the great majority of doctors and scientific authors consider that the efficacy of first-generation antidepressants (imipramine, amitriptyline, nortriptyline) has been proved beyond any reasonable doubt, and that efficacy also has been demonstrated for newer products such as trazodone, the selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake... 

A larger set of placebo-controlled studies show conclusively that imipramine is also effective for the treatment of panic disorders. Other agents shown to be effective in panic disorders include the SSRIs paroxetine, sertraline, fluvoxamine, fluoxetine and citalopram. Generally, initial treatment of moderate to severe panic disorders may require the initiation of a short course of benzodiazepines e.g. clonazepam (0.5 1 mg twice daily), and an SSRI. The patient will obtain immediate relief from panic attacks with the benzodiazepine whereas the SSRI may take 1 6 weeks to become effective. Once a patient is relieved of initial panic attacks, clonazepam should be tapered and discontinued over several weeks and SSRI therapy continued thereafter. There are no pharmacological treatments available for specific phobias, however controlled trials have shown efficacy for several agents, e.g. phenelzine, moclobemide. clonazepam, alprazolam, fluvoxamine. sertraline and paroxetine in the treatment of social phobia (Roy-Byrne and Cowlev, 2002). 

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