Imipramine panic disorder

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

Tricyclic Antidepressants (TCAs). The TCAs, particularly imipramine (Tofranil), were also discovered soon after their introduction to be effective in the treatment of panic attacks. Imipramine, the best-studied TCA in the treatment of panic disorder, is most often helpful at daily doses of 150-250 mg, though it must be started at 10-25 mg, usually at bedtime, and gradually increased over 2-4 weeks. Although they are not as well studied, many clinicians prefer to use the secondary amine TCAs, desipramine (Norpramin) and nortriptyline (Pamelor), because they have milder side effects than imipramine. Clomipramine (Anafranil), though probably the TCA with the greatest side effect burden, is often said to be most effective in patients with refractory disease. 

Tricyclic Antidepressants (TCAs). Because of their effectiveness not only for depression but for anxiety disorders such as panic disorder as well, TCAs were the first medications formally tested in the treatment of PTSD. Three TCAs, amitriptyline, imipramine, and desipramine, have been studied in small trials, producing modest benefit for reexperiencing and hyperarousal symptoms, without any relief of avoidance/numbing symptoms. Given this limited benefit in conjunction with the side effect burden and potential for toxicity in a suicide prone population, TCAs are infrequently used in the treatment of PTSD. Please refer to Chapter 3 for more information regarding TCAs. 

Flint J, Corley R, De Fries JC, Fulker DW, Gray JA, MUler S, Collins AC (1995) A simple genetic basis for a complex psychological trait in laboratory mice. Science 269 1432-1435 Fontana DJ, Commissaris RL (1988) Effects of acute and chronic imipramine administration on conflict behavior in the rat a potential animal model for the study of panic disorder Psychopharmacology (Berl) 95 147-150... 

Nalepa I, Kreiner G, Kowalska M, Sanak M, Zelek-Molik A, Vetulani J (2002) Repeated imipramine electroconvulsive shock increase alpha(lA)-adrenoceptor mRNA level in rat prefrontal cortex. Eur J Clin Pharmacol 444 151-159 Nesse RM, Ciu-tis GC, Thyer BA, McCann DS, Huber-Smith MJ, Knopf RF (1985) Endocrine and cardiovascular responses during phobic anxiety. Psychosom Med 47 320-332 Nisenbaiun LK, Zigmund MJ, Sved AF, Abercrombie ED (1991) Prior exposure to chronic stress results in enhanced synthesis and release of hippocampal norepinephrine in response to a novel stressor. J Neurosci 11 1473-1484 Nutt DJ (1989) Altered alpha2-adrenoceptor sensitivity in panic disorder. Arch Gen Psychiatry 46 165-169... 

Imipramine, a TCA, was the first pharmacological agent noted to treat panic disorder (Klein 1964). Other TCAs, notably clomipramine, have also been found to have significant anxiolytic properties (den Boer et al. 1990 Modigh 1992). Studies of ethnic differences in the pharmacokinetics of the TCAs in... 

Modigh K, Westberg P, Eriksson E (1992) Superiority of clomipramine over imipramine in the treatment of panic disorder a placebo-controlled trial. J Clin Psychopharmacol 12 251-261... 

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... 

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. 

Barlow DH, Gorman JM, Shear MK, Woods SW (2000) Cognitive-behavioral therapy, imipramine, or their combination for panic disorder a randomized controlled trial. JAMA 283 2529-2536... 

Frank JB, Kosten TR, Giller EL Jr, Dan E (1988) A randomized clinical trial of phenelzine and imipramine for posttraumatic stress disorder. Am J Psychiatry 145 1289-1291 Goddard AW, Brouette T, Almai A, Jetty P, Woods SW, Charney D (2001) Early coadministration of clonazepam with sertraline for panic disorder. Arch Gen Psychiatry 58 681-686 Goodnick PJ, Goldstein BJ (1998) SSRIs in affective disorders. I. Basic pharmacology. J Psychopharmacol 12(Suppl B) S5-S20... 

Ware, M.R. and DeVane, C.L. (1990) Imipramine treatment of panic disorder during pregnancy. / Clin Psychiatry 51 482 84. 

Because many antidepressant compounds are also effective in panic disorder, we performed a trial of inositol in panic (Benjamin et al. 1995). Twenty-one patients with panic disorder with or without agoraphobia completed a double-blind, random assignment crossover treatment trial of inositol 12 g/ day versus placebo, with 4 weeks in each treatment phase. Frequency of panic attacks and severity of panic disorder and of agoraphobia declined significantly more on inositol than on placebo the effect was comparable to that of imipramine in previous studies. Side effects were minimal. 

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... 

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... 

Note. BROF = brofaromine CIT = citalopram CLO = clomipramine CT = cognitive therapy Dx = diagnosis EXP = exposure in vivo FLU = fluvoxamine FLUOX = fluoxetine GAD = generalized anxiety disorder 5-HTP = 5-hydrox3rtryptophan IMl = imipramine MAP = maprotiline OCD = obsessive-compulsive disorder PAR = paroxetine PD = panic disorder PLA = placebo PPM = psychological panic management RIT = ritanserin ... 

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-... 

Bakish D, Saxena BM, Bowen R, et al Reversible monoamine oxidase-A inhibitors in panic disorder. Clin Neuropharmacol 16 (suppl 2 S77-S82, 1993a Bakish D, Lapierre Y, Weinstein R, et al Ritanserin, imipramine and placebo in the treatment of dysthymic disorder. J Chn Psychopharmacol 13 409-414, 1993b Bakish D, Ravindran A, Hooper C, et al Psychopharmacological treatment response of patients with a DSM-111 diagnosis of dysthymic disorder. Psychopharmacol Bull 30 53-59, 1994... 

Bakish D, Hooper CL, Filteau MJ, et al A double-blind placebo-controlled trial comparing fluvoxamine and imipramine in the treatment of panic disorder with or without agoraphobia. Psychopharmacol Bull 32 135-141, 1996 Bakish D, Hooper CL, Thorton MD, et al Fast onset an open study of the treatment of major depressive disorder with nefazodone and pindolol combination therapy. Int Clin Psychopharmacol 12 91-97, 1997 Baldwin DS Depression and sexual function. J Psychopharmacol 10 (suppl l) 30-34, 1996... 

Bradwejn J, Koszycki D Imipramine antagonizes the panicogenic effects of CCK-4 in panic disorder patients. Am J Psychiatry 151 261-263, 1994b... 

Cassano GB, Petracca A, Parugi G, et al Clomipramine for panic disorder, I the first 10 weeks of a long-term comparison with imipramine. J Affect Disord 14 123-127, 1988... 

Papp LA, Klein DF, Gorman JM Carbon dioxide hypersensitivity, hyperventilation, and panic disorder. Am J Psychiatry 150 1149-1157, 1993 Papp M, Klimek V, Willner P Parallel changes in dopamine D2 receptor binding in limbic forebrain associated with chronic mild stress-induced anhedonia and its reversal by imipramine. Psychopharmacology 115 441-446, 1994 Parasuraman R, Haxby JV Attention and brain function in Alzheimer s disease. Neuropsychology 7 242-272, 1993... 

Pohl RB, Wolkow RM, Clary CM Sertraline in the treatment of panic disorder a double-bhnd multicenter trial. Am J Psychiatry 155 1189-1195, 1998 Poirer MF, Galzin AM, et al Short-term hthium administration to healthy volunteers produces long-lasting pronounced changes in platelet serotonin uptake but not imipramine binding. Psychopharmacology 94 521-526, 1988 Poiiier-littre MF, Loo FI, Dennis T, et al Dthium treatment increases norepinephrine turnover in the plasma of healthy subjects (letter). Arch Gen Psychiatry 50 72-73, 1993... 

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... 

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). 

Starting with a standard TCA such as imipramine, a typical dose is 25 mg three times daily. Dose may be increased by 25 mg every 2 or 3 days, as tolerated, and can usually be increased to 150 mg per day by the end of the first week in healthy adults. The elderly, medically compromised, those hypersensitive to side effects, or those with associated panic disorder may require lower doses and more gradual increases (see discussion in Chapter 6). 

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. 

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. 

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. 

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. 

Mavissakalian M, Perel JM. Protective effects of imipramine maintenance treatment in panic disorder with agoraphobia. Am J Psychiatry 1992 149 1053-1057. 

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. 

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