Clomipramine panic disorder

Obsessive-compulsive disorder may be linked to abnormalities of the neurotransmitters serotonin and dopamine. The neuroanatomical basis of OCD may be related to dysfunction in the basal ganglia. The hallmark of treatment for OCD is use of SSRIs plus the tricyclic antidepressant clomipramine. Panic disorder is characterized by unexpected panic attacks, possibly linked to abnormalities in the neurotransmitters norepinephrine and GABA, in the sensitivity of benzodiazepine receptors, or even in the regulation of respiration. Drag treatments include SSRIs, several of the newer antidepressants, high-potency benzodiazepines, many tricyclic antidepressants, and MAO inhibitors. 

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. 

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... 

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. 

Lecrubier Y, Judge R (1997) Long-term evaluation of paroxetine, clomipramine and placebo in panic disorder. Collaborative Paroxetine Panic Study Investigators. Acta Psychiatr Scand 95 153-160... 

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 ... 

Citalopram and fluoxetine also have been studied in panic disorder (Michelson et al. 1998 Wade et al. 1997). Citalopram was compared with clomipramine. At the most effective citalopram dose (20-30 mg/day), approximately 58% of patients were panic-free compared with 50% of patients receiving clomipramine and 32% of placebo patients. All rating scales suggested that 20 or 30 mg/day of citalopram was more effective than 40 or 60 mg/day of citalopram. Finally, data support the efficacy of fluoxetine in panic disorder. In a study comparing 10 and 20 mg/day of fluoxetine and placebo, fluoxetine treatment, particularly the 20-mg daily dose, was associated with more improvement than placebo across multiple measures, including functional impairment. 

Based on some intriguing case reports (Jenike et al. 1983), a trial with a monoamine oxidase inhibitor (MAOI) may be an option in OCD patients who have comorbid panic disorder. In a double-blind trial, both phenelzine and clomipramine were found to be effective in reducing symptoms in OCD, as reflected on two of four OC measures [Vallejo et al. 1992). None of the patients in this study had panic disorder. This study suggests that MAOIs may be helpful in some patients with OCD even in the absence of panic disorder. However, in an earlier comparison trial, clomipramine, but not the MAOI clorgiline, resulted in significant reduction in OC symptoms [Insel et al. 1983b). Additional studies are needed to evaluate the place of MAOIs (including the newer reversible inhibitors of monoamine oxidase A [RIMAs], such as moclobemide) in the pharmacotherapy of OCD. 

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... 

Joyce D, Hurwitz HMB Avoidance behaviour in the rat after 5-hydroxytryptophan (5-HTP) administration. Psychopharmacologia 5 424-430, 1964 Joyce EM The neurochemistry of Korsakoff s syndrome, in Cognitive Neurochemistry. Edited by Stahl SM, Iversen SD, Goodman EC. Oxford, England, Oxford Science Publications, 1987, pp 327-345 Judd EK, Chua P, Lynch C, et al Eenfluramine augmentation of clomipramine treatment of obsessive compulsive disorder. Aust N Z J Psychiatry 25 412-414, 1991 Judge R, Steiner M The long-term efficacy and safety of paroxetine in panic disorder. 

Lecrubier Y, Judge R Long-term evaluation of paroxetine, clomipramine and placebo in panic disorder. Acta Psychiatr Scand 95 153-160, 1997 Lecrubier Y, Puech AJ, Azcona A, et al A randomized double-blind placebo-con-trolled study of tropisetron in the treatment of outpatients with generalized anxiety disorder. Psychopharmacology 112 129, 1993 Lecrubier Y, Pletan Y, Selles A, et al Clinical efficacy of milnacipran placebo-con-trolled trials. Int Chn Psychopharmacol 11 (suppl 4 29-34, 1996 Lecrubier Y, Bakker A, Dunbar G, et al A comparison of paroxetine, clomipramine and placebo in the treatment of panic disorder. Acta Psychiatr Scand 95 145-152, 1997... 

McTavish D, Benfield P Clomipramine an overview of its pharmacological properties and a review of its therapeutic use in obsessive compulsive disorder and panic disorder. Drugs 39 136-153, 1990... 

Bakker A, van Dyck R, Spinhoven P, et al. Paroxetine, clomipramine, and cognitive therapy in the treatment of panic disorder. J Clin Psychiatry 1999 60 831-838. 

By the 1970s and early 1980s it was recognized that certain tricyclic antidepressants and monoamine oxidase (MAO) inhibitors were effective in treating panic disorder and one tricyclic antidepressant (clomipramine) was effective in treating obsessive-compulsive disorder. Thus, there began to be recognized that some antidepressants overlapped with anxiolytics for the treatment of anxiety disorder sub-types or for mixtures of anxiety and depression (Fig. 8—8). However, either anxiolytics... 

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. 

Besides depression, clomipramine is also widely used in the treatment of phobic and obsessive-compulsive disorders (6-8) and in panic disorders (9). 

Treatment. The choice lies between a fast-acting benzodiazepine such as alprazolam (1-3 mg/day p.o.) and a drug with delayed efficacy but fewer problems of withdrawal such as a TCA, e.g. clomipramine (100-250 mg/day p.o.) or an SSRI, e.g. paroxetine (20-50 mg/day p.o.). The different time course of these two classes of agent in panic disorder is depicted in Fig. 19.5 (see also Tables 19.5 and 19.6). 

Clomipramine and imipramine demonstrated to benefit panic disorder. 

I RCTs have demonstrated efficacy of TCAs for anxiety associated with depression, GAD, panic disorder (clomipramine, imipramine) and OCD (clomipramine only). 

Four patients taking tricyclic antidepressants (imipramine, clomipramine, dibenzepin) and one taking viloxazine relapsed into depression when they took co-trimoxazole (trimethoprim with sulfamethoxazole) for 2 to 9 days. The reasons are not known. Another patient treated for 5 years with alprazolam and imipramine for panic disorder and who had not had panic attacks for several months developed insomnia, anxiety and panic attacks within 6 days of starting to take co-trimoxazole. The panic... 

Drugs used in obsessive-compulsive disorders and panic attacks clomipramine... 

Uses include major depressions, phobic and panic anxiety states, neuropathic pain, enuresis, and obsessive-compulsive disorder (OCD) (clomipramine now backup). Withdrawal syndrome follows discontinuance in depression—nausea, headache, vertigo, malaise, nightmares. 

Other clinical uses Tricyclic drugs are also used in the treatment of bipolar affective disorders, acute panic attacks, phobic disorders (compare with alprazolam Chapter 22), enuresis, and chronic pain states. Clomipramine and the selective serotonin reuptake inhibitors, including fiuvoxamine, are effective in obsessive-compulsive disorders. SSRls are also effective in patients who suffer from panic attacks, social phobias, bulimia, and premenstrual syndrome (PMS) and may also be useful in the treatment of alcohol dependence. Bupropion is used for management of patients attempting to withdraw from nicotine dependence. 

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