Imipramine Alprazolam

Feighner JP, Aden GC, Fabre LF, et al. Comparison of alprazolam, imipramine and placebo in the treatment of depression. JAMA 1984 249 3057-3064. 

Cross-National Collaborative Panic Study, Second Phase Investigators. Drug treatment of panic disorder. Comparative efficacy of alprazolam, imipramine, and placebo. BrJ Psychiatry 1992 160 191-202. 

Andersch S, Rosenberg NK, Kullingsjo H, Ottosson JO, Bech P, Bruun-Hansen J, Hanson L, Lorentzen K, Mellergard M, Rasmussen S, et al. Efficacy and safety of alprazolam, imipramine and placebo in treating panic disorder. A Scandinavian multicenter study. Acta Psychiatr Scand 1991 365(Suppl) 18-27. 

Panic disorder SSRIs Venlafaxine XR Alprazolam Clomipramine Clonazepam Imipramine Phenelzine... 

Boyer W (1995) Serotonin uptake inhibitors are superior to imipramine and alprazolam in alleviating panic attacks a metaanalysis. Int Clin Psychopharmacol 10 45-49 Bradwejn J, Koszycki D (1994) Imipramine antagonism of the paniogenic effects of chole-cystokinin tetrapeptide in panic disorder patients. Am J Psychiatry 151 261-263 Bradwejn J, Koszycki D, Paradis M, Reece P, Hinton J, Sedman A (1995) Effect of CI-988 on cholecystokinin tetrapeptide-induced panic symptoms in healthy volunteers. Biol Psychiatry 38 742-746... 

Lenox RH, Shipley JE, Peyser JM, Williams JM, Weaver LA (1984) Double-blind comparison of alprazolam versus imipramine in the inpatient treatment of major depressive illness. Psychopharmacol Bull 20 79-82... 

A meta-analysis (Boyer 1995) has compared some serotonin reuptake inhibitors (paroxetine, fluvoxamine, zimeldine, and clomipramine) with imipramine and alprazolam in the alleviation of panic attacks in patients with DSM-III or DSM-III-R panic disorder. Although all three classes of drugs were shown to be significantly more effective than placebo, the serotonin reuptake inhibitors were also significantly superior to both imipramine and alprazolam. The findings of this meta-analysis highlight the importance of... 

A second issue relating to long-term medication is the effect of withdrawing medication at the end of a period of treatment. Benzodiazepines are associated with discontinuation symptoms, and their repeated use may foster the development of true physiological dependence. In a study of discontinuation of treatment for panic disorder [Rickels et al. 1993) with either alprazolam [n = 27), imipramine [n = 11) or placebo [n = 10), a withdrawal syndrome was observed in almost all patients treated with alprazolam but in few pa-... 

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). 

Keller MB, Lavori PW, Goldenberg IM, et al. Influence of depression on the treatment of panic disorder with imipramine, alprazolam and placebo. J Affect Disord 1993 28 27-38. 

Goldberg SC, Ettigi P, Schulz PM, et al. Alprazolam versus imipramine in depressed out-patients with neurovegetative signs. J Affect Disord 1986 11 139-145. 

Wells BG, Evans RL, Ereshefsky L, et al. Clinical outcome and adverse effect profile associated with concurrent administration of alprazolam and imipramine. J Clin Psychiatry 1988 49 394-399. 

Alprazolam was also compared with imipramine and placebo in a sample of 1,168 randomly assigned subjects in the Cross-National Collaborative Panic Study, Phase Two. This study was conducted at 12 centers and assessed clinical change over 8 weeks of double-blind treatment. Improvement occurred with alprazolam by weeks 1 and 2 and with imipramine by week 4. By the end of week 8, the effects of the two active drugs were similar and both were superior to placebo for most outcome measures (31). 

Like alprazolam, clonazepam may cause treatment-emergent depression in some patients. Pollack et al. (42) also reported that only 10% of their patients who remained on clonazepam had a history of depression, although 47% lost to follow-up and 30% who eventually required alternate treatment had histories of dysthymia or depression. Of 31 patients without a prior history of affective illness, depression developed in three on low daily dosages (0.75, 1.5, and 2 mg), one was switched to alprazolam, and the others responded to the addition of desipramine or imipramine. These investigators recommend that, until further data are available, PD patients with chronic or concurrent depression should not be given clonazepam alone and that those in whom depression develops during clonazepam therapy should have their dose lowered or an adjunctive antidepressant added. 

Most studies comparing imipramine and alprazolam indicate that both drugs produce a comparable reduction of symptoms, although onset of action is considerably slower with a TCA, requiring 2 weeks to as long as 12 weeks (21,24, 26, 37, 85, 92). 

SSRIs sometimes cause an initial jitteriness similar to that noted with initial imipramine therapy for PD. This may be more common with SSRIs than with other currently available non-TCA antidepressant therapies for PD. Just as low initial imipramine doses avert this reaction, initiating SSRI therapies with one fourth to one half the usual starting antidepressant dose followed by gradual increments with low doses can avert this reaction. This syndrome can also be blocked by add-on, low-dose, as-needed BZD therapy (e.g., alprazolam or lorazepam). 

Charney DS, Woods SW, Goodman WK, et al. Drug treatment of panic disorder the comparative efficacy of imipramine, alprazolam, and trazodone. J Clin Psychiatry 1986 47 580-586. 

Riziey R, Kahn RJ, McNair DM, et al. A comparison of alprazolam and imipramine in the treatment of agoraphobia and panic disorder. Psychopharmacol Bull 1986 22 167-172. 

Uhlenhuth EH, Matuzas W, Glass RM, et al. Response of panic disorder to fixed doses of alprazolam or imipramine. J Affect Disord 1989 17 261-270. 

Schweizer E, Rickels K, Weiss S, et al. Maintenance drug treatment of panic disorder. I. Results of a prospective, placebo-controlled comparison of alprazolam and imipramine. Arch Gen Psychiatry 1993 50 51-60. 

Fyer AJ, Liebowitz MR, Gorman JM, et al. Comparative discontinuation of alprazolam and imipramine in panic patients. Presented at the Annual Meeting of the ACNP, San Juan, Puerto Rico, December 1988. 

Hoehn-Saric R, McLeod DR, Zimmerli WD (1988) Differential effects of alprazolam and imipramine in generalized anxiety disorder Somatic versus psychic symptoms. J Clin Psychiatry 49 293-301... 

Clinically important, potentially hazardous interactions with alprazolam, amphetamines, astemizole, clarithromycin, clozapine, desipramine, dexibuprofen, dextroamphetamine, diethylpropion, droperidol, duloxetine, erythromycin, haloperidol, imipramine, isocarboxazid, linezolid, lithium, MAO inhibitors, mazindol, meperidine, methamphetamine, midazolam, moclobemide, nortriptyline, phendimetrazine, phenelzine, phentermine, phenylpropanolamine, phenytoin, pimozide, pseudoephedrine, selegiline, serotonin agonists, sibutramine, St John s wort, sumatriptan, sympathomimetics, tramadol, tranylcypromine, trazodone, tricyclic antidepressants, troleandomycin, tryptophan, zolmitriptan... 

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