Fluvoxamine Clomipramine

Drug therapies include tricyclic antidepressants and SSRIs. Treatment should be continued for at least 29 weeks. Nortriptyline, amitriptyline, clomipramine, desipramine, fluvoxamine, and bupropion have been used successfully. 

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. 

Palego L, Marazziti D, Biondi L, Giannaccini G, Sarno N. 2000. Simultaneous plasma level analysis of clomipramine, N-desmethylclomipramine, and fluvoxamine by reversed-phase liquid chromatography. Ther Drug Monit 22(2) 190-194. 

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. 

A potential limitation of most of the controlled studies discussed above relates to the numerous exclusion criteria used for patient selection. For example, in order to find homogenous samples, major depression, bipolar disorder, Tourette s disorder, psychosis (clomipramine, fluvoxamine and fluoxetine trials), primary psychiatric disorder other than OCD (clomipramine and sertraline trials), and attention deficit/hyperactivity disorder (ADHD), autism, or other developmental disorders (clomipramine and fluoxetine trials) were excluded. Thus it remains unknown how well these controlled studies will generalize to more naturalistic clinical populations that are highly comorbid and where exclusion criteria are not applied. 

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). 

Clomipramine, fluvoxamine, and sertraline labeling all describe positive results of trials of these drugs in pediatric patients with OCD, in effect, granting an indication for these drugs in pediatric OCD. 

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 ... 

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. 

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. 

Ottevanger EA. Fluvoxamine and clomipramine in depressed hospitalized patients results from a randomized, double-blind study. Encephale 1995 21 317-321. 

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. 

Goodman has opined that the backbone of pharmacologic treatment for OCD is a 10- to 12-week trial with an SRI in adequate doses. In most cases, treatment should be initiated with an SSRI because of the superior safety, tolerability, and equivalent efficacy of this class of drugs compared with clomipramine ( 195). Fluoxetine, sertraline, fluvoxamine, and paroxetine have, in separate multicenter trials, demonstrated efficacy and tolerability in the treatment of OCD ( 196). Citalopram, a recently marketed SSRI, also should be effective in the treatment of OCD (197). 

The primary question for this meta-analysis was whether the high-potency SRIs are differentially effective in OCD. Because we cannot argue for greater efficacy of SRIs over placebo if they are only shown to be superior to standard antidepressants (because we do not know whether any antidepressant would be more effective than placebo), we also performed meta-analyses of those studies comparing individual SRIs (i.e., clomipramine, fluvoxamine), as well as all SRIs, with placebo. 

The meta-analysis of all studies comparing clomipramine or SRIs with placebo for the treatment of OCD found that the active drug produced a better result in every trial. We then calculated the effect size and the statistical significance for clomipramine alone and fluvoxamine alone. Their results showed a highly significant effect for both drugs (Table 13-10 and Table 13-11). There were also several studies with sertraline, fluoxetine, and paroxetine that demonstrated similar results (219, 220, 221, 222. 223,. 224, 225 and 226). 

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