Paroxetine Clomipramine

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... 

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... 

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. 

Acetylsalicylic acid, ibuprofen, fenoprofen, naproxen, diclofenac, ketoprofen in 26 min Fluoxetine, venlafaxine, citalopram, sertraline, paroxetine, clomipramine, trazodone in 17 min... 

Antidepressants are used in the treatment of neuropathic pain and headache. They include the classic tricyclic compounds and are divided into nonselective nor-adrenaline/5-HT reuptake inhibitors (e.g., amitriptyline, imipramine, clomipramine, venlafaxine), preferential noradrenaline reuptake inhibitors (e.g., desipramine, nortriptyline) and selective 5-HT reuptake inhibitors (e.g., citalopram, paroxetine, fluoxetine). The reuptake block leads to a stimulation of endogenous monoaminer-gic pain inhibition in the spinal cord and brain. In addition, tricyclics have NMDA receptor antagonist, endogenous opioid enhancing, Na+ channel blocking, and K+ channel opening effects which can suppress peripheral and central sensitization. Block of cardiac ion channels by tricyclics can lead to life-threatening arrhythmias. The selective 5-HT transporter inhibitors have a different side effect profile and are safer in cases of overdose [3]. 

Decision analytic models have been constmcted to compare the costs of TCAs with those of SSRIs and other compounds. These comparisons have included imipramine or amitriptyline versus paroxetine or sertraline (Stewart, 1994) imipramine versus paroxetine Qonsson and Bebbington, 1994 McFarland, 1994 Lapierre et al, 1995) fluoxetine versus amitriptyline, clomipramine, doxepin and imipramine (Le Pen et al, 1994) venlafaxine versus amitriptyline, desipramine. 

Tricyclic drugs have, as the name implies, a three-ring structure, and interfere with reuptake of norepinephrine and/or serotonin into axon terminals. Tricyclic drugs include imipramine (Tofranil), amitriptyline (Elavil), clomipramine (Anafranil), and nortriptyline (Pamelor, Aventil). Tricyclics have the occasional but unfortunate cardiovascular side effects of arrhythmia and postural hypotension. Newer, nontricyclic antidepressants have been developed that are collectively referred to as SSRIs. These have a potent and selective action on serotonin, and lack the cardiovascular side effects of the tricyclics. These include fluoxetine (Prozac), paroxetine (Paxil), sertraline (Zoloft), and fluvoxamine (Luvox). A fifth SSRI, citalopram (Celexa) has been used in Europe and has recently been approved in the United States. Venlafaxine (Effexor) blocks reuptake of norepinephrine and serotonin, while bupropion (Wellbutrin) acts on both dopamine and norepinephrine. 

SRI Citalopram Clomipramine Fluoxetine Fluvoxamine Paroxetine Sertraline... 

Amitriptyline, clomipramine, imipramine, desipramine, nortriptyline, trimipramine, AT-desmethylclomipramine, fluvoxamine, norfluoxetine, paroxetine, venlafaxine, sertraline Neuroleptics... 

The prototypical serotonin reuptake inhibitor (SRI) medication is the non-selective agent clomipramine, a tricyclic antidepressant (TCA). The Selective SRIs (SSRIs) include fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), fluvoxamine (Luvox), and citalo-pram (Celexa). The Food and Drug Administration (FDA) approved clinical indications for these medications are described in Table 22.1. 

FIGURE 39.2 Treatment algorithm for pediatric obsessive-compulsive disorder (OCD). In adjusting cognitive behavior therapy (CBT), increase frequency or intensity, or alter the setting or format, e.g., have it be home based or day treatment. CMI, clomipramine DMI, desipramine NT, nortriptyline SSRI, selective serotonin reuptake inhibitor (fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram). 

In most cases, SSRIs are the first choice for drugs to combat OCD. Clomipramine, fluvoxamine, fluoxetine, paroxetine, sertraline, and citalopram are all SSRIs that have been proven effective in reducing OCD symptoms. However, in about 40 to 60% of patients, these drugs do not completely alleviate all the symptoms. When this is the case, a second type of drug called a neuroleptic is often added. Neuroleptic drugs, such as haloperidol, clozapine, risperidone, and chlorpromazine... 

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 ... 

Extensive databases [see Table 24-1) have now shown that paroxetine and sertraline can reduce panic attacks to zero and prevent relapse. Paroxetine studies constitute the largest data set more than 700 patients have been treated for periods ranging from 10 to 36 weeks. In the placebo-controlled comparisons with clomipramine, paroxetine had an earlier onset of action and was better tolerated than clomipramine. Paroxetine was significantly better than placebo from week 4 onward, whereas no separation was seen between clomipramine and placebo until the end of the study. Fewer withdrawals occurred as a result of adverse events with paroxetine (7.3%) than with either clomipramine (14.9%) or placebo (11.4%). The minimum dose shown to be superior to placebo was 40 mg/day. 

Paroxetine and placebo had similar tolerability, whereas clomipramine was less well tolerated, with more patients withdrawn from treatment as a result of emergent adverse events. Holland et al. (1994) reported on the effects of long-term treatment with fluvoxamine in patients who had completed a double-blind study. Patients who were transferred from placebo to fluvoxamine and those who continued taking fluvoxamine showed continued improvement in efficacy parameters. 

Danish University Antidepressant Group Paroxetine a selective serotonin reuptake inhibitor showing better tolerance but weaker antidepressant effect profile in comparison with clomipramine a controlled multicentre study. J Affect Disord 18 289-299, 1990... 

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. 

Another approach to correct neurotransmission is to inhibit the reuptake of the neurotransmitters into their presvnaptic endings. If the presynaptic reuptake mechanism of a neurotransmitter is blocked then more of the neurotransmitter will stay in the synaptic cleft and be functionally available. Many antidepressant drugs, called reuptake inhibitors , are thought to act via this mechanism. If selective for serotonin they are called selective serotonin reuptake inhibitors (SSRIs, Chapter 1), but if selective for both serotonin and noradrenaline they are called serotonin noradrenaline reuptake inhibitors (SNRIs). Most older antidepressants, such as the tricyclic compounds amitriptyline, imipramine and clomipramine, have little specificity for any of the neurotransmitters fluoxetine, paroxetine, citalopram and a few others are specific for serotonin venlafaxine is a representative of the SNRIs. A more recent mixed-uptake inhibitor is mirtazepine, and some similar compounds are about to be launched. 

Treatment of GAD can be undertaken using a number of pharmacological agents. Benzodiazepines have been found to be superior to placebo in several studies and all benzodiazepines appear to be equally effective. However, side effects include sedation, psvchomotor impairment, amnesia and tolerance (Chapter 1). Recent clinical data indicate that SSRIs and SNRIs are effective in the treatment of acute GAD symptoms. Venlafaxine, paroxetine and imipramine have been shown to be effective antianxiety medications in placebo-controlled studies. Case studies also indicate the usefulness of clomipramine, nefazodone, mirtazapine, fluoxetine and fluvoxamine in GAD. Buspirone, a 5-HTla receptor partial agonist, has been shown to be effective in several placebo-controlled, double-blind trials (Roy-Byme and Cowley, 2002). Buspirone has a later onset of action than both benzodiazepines and SSRIs but with the advantage of being non-addictive and non-sedating. 

With this caveat in mind, each side of the debate has evidence to support its position. The evidence is first summarized supporting the position that SSRIs are less effective than are some other antidepressants (particularly those with dual effects on both serotonin and NE CNS systems) in patients with more severe depression or who are hospitalized. Danish investigators in two double-blind, active-controlled studies found that clomipramine produced a superior response with either paroxetine or citalopram in the treatment of patients hospitalized for major depression (116, 117). Two double-blind studies also have shown that venlafaxine and mirtazapine were more effective than fluoxetine in patients hospitalized with depression ( 114,118). Finally, there are studies showing that the addition of desipramine (one of the most selective NE reuptake inhibitors) to an SSRI can convert nonresponders or pamal responders to full response ( 119, 119a, 120). 

Patient with obsessive-compulsive symptoms (or disorder) is nonresponsive on adequate blood levels consider clomipramine or an SSRI (e.g., fluoxetine, sertraline, paroxetine). 

All SSRIs have an antipanic effect. Their advantages are limited adverse effects and lack of toxicity. Because of more acceptable adverse effect profiles, the SSRIs are usually the drugs of choice. Several studies consistently indicate that SSRIs such as fluoxetine, sertraline, paroxetine, fluvoxamine, as well as agents such as clomipramine and trazodone, all possess antipanic efficacy, although the last may be less effective than imipramine ( 24, 105, 106, 107, 108 and 109). 

Fluoxetine, paroxetine, fluvoxamine, and citalopram, as well as clomipramine, have been shown in placebo-controlled, double-blind studies to be safe and effective antipanic drugs for shortterm PD therapy. Evidence also is accumulating to suggest that these drugs may be effective for long-term panic treatment, but more data are needed to confirm this. 

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