Depression fluvoxamine

Zimelidine was the first serotonin reuptake inhibitor available for clinical use, but in 1982 was withdrawn worldwide because of its toxicity ( 110). Despite this initial setback, five members of this class have been marketed in the United States and various countries around the world citalopram (Celexa), fluoxetine (Prozac), fluvoxamine (Luvox), paroxetine (Paxil), and sertraline (Zoloft). All except fluvoxamine have marketed indications in the United States for the treatment of major depression. Fluvoxamine is marketed in the United States for the treatment of obsessive-compulsive disorder rather than major depression, although it is marketed in a number of other countries for major depression. 

A 45-year-old woman taking phenytoin 300 mg/day had a plasma phenytoin concentration of 66 pmol/1 (29). When she became depressed fluvoxamine 50 mg/day was added. A month later her depressive symptoms had improved, but she was ataxic and the plasma phenytoin concentration was 196 pmol/1. The fluvoxamine was withdrawn and the phenytoin dose reduced to 150 mg/day. Her plasma phenytoin concentration fell to 99 pmol/1, with resolution of the ataxia. 

SSRIs are widely used for treatment of depression, as well as, for example, panic disorders and obsessive—compulsive disorder. These dmgs are well recognized as clinically effective antidepressants having an improved side-effect profile as compared to the TCAs and irreversible MAO inhibitors. Indeed, these dmgs lack the anticholinergic, cardiovascular, and sedative effects characteristic of TCAs. Their main adverse effects include nervousness /anxiety, nausea, diarrhea or constipation, insomnia, tremor, dizziness, headache, and sexual dysfunction. The most commonly prescribed SSRIs for depression are fluoxetine (31), fluvoxamine (32), sertraline (52), citalopram (53), and paroxetine (54). SSRIs together represent about one-fifth of total worldwide antidepressant unit sales. 

Indeed, 5-HT is also a substrate for the 5-HT transporter, itself an important player in the treatment of depression, and more recently for the whole range of anxiety disorders spectrum (GAD, OCD, social and other phobias, panic and post-traumatic stress disorders). It is the target for SSRIs (selective serotonin reuptake inhibitors) such as fluoxetine, paroxetine, fluvoxamine, and citalopram or the more recent dual reuptake inhibitors (for 5-HT and noradrenaline, also known as SNRIs) such as venlafaxine. Currently, there are efforts to develop triple uptake inhibitors (5-HT, NE, and DA). Further combinations are possible, e.g. SB-649915, a combined 5-HTia, 5-HT1b, 5-HT1d inhibitor/selective serotonin reuptake inhibitor (SSRI), is investigated for the treatment of major depressive disorder. 

Yoshida, K., Ito, K. etal. (2002). Influence of the serotonin transporter gene-linked polymorphic region on the antidepressant response to fluvoxamine in Japanese depressed patients. Prog. Neuropsychopharmacol. Biol. Psychiatry, 26(2), 383-6. 

Zanardi, R., Serretti, A. etal. (2001). Factors affecting fluvoxamine antidepressant activity influence of pindolol and 5-HTTLPR in delusional and nondelusional depression. Biol. Psychiatry, 50(5), 323-30. 

Sato, K., Yoshida, K., Takahashi, H. etal. (2002). Association between -1438G/A promoter polymorphism in the 5-HT(2A) receptor gene and fluvoxamine response in Japanese patients with major depressive disorder. Neuropsychobiology, 46, 136-40. 

Maprotiline, Moclobemide, Mianserin, Fluoxetine (Prozac), Paroxetine, Sertraline, Fluvoxamine, Citalopram, Venlafaxin (generic IR formulation and the brand Venlafaxine XR), Mirtazapine, Flupentixol-melitracen (Deanxit), Tianeptine, Extract of St. John s Wort, Buspirone Depression and anxiety... 

Alternatively, the current antidepressant may be augmented (potentiated) by the addition of another agent (e.g., lithium, T3), or an atypical antipsychotic (e.g., risperidone). Risperidone has been shown to be effective in combination with fluvoxamine, paroxetine, or citalopram in treatment-resistant depression. Olanzapine and fluoxetine have been found to be safe and effective in treatment-resistant depression. 

Since the introduction of the first approved SSRI, fluoxetine (1) in 1987 [9], a number of SSRIs have been developed for the treatment of depression [2], Currently, the five most commonly prescribed SSRIs are fluoxetine, escitalopram (2, S-enantiomer of citalopram), sertraline (3), paroxetine (4) and fluvoxamine (5). Recent effort in the clinical development of new SSRIs has focused on the treatment of premature ejaculation (PE) by taking advantage of the ejaculation-delaying side effects of SSRIs [10]. Although SSRIs have been prescribed off-label to treat this condition, an SSRI with rapid onset of action and rapid clearance could be preferred for on-demand treatment of PE [11,12]. Dapoxetine (LY210448, 6), an... 

In 1983, the first SSRI, fluvoxamine (Luvox), debuted in Switzerland. Five years later, fluoxetine (Prozac) was introduced in the United States. The SSRIs revolutionized the treatment of depression. They improved safety and tolerability, removing much of the stigma of taking an antidepressant. In fact, some think that it has become too easy to take antidepressants and that psychotherapy is being neglected or discouraged. 

The current SSRIs in the United States inclnde fluoxetine, fluvoxamine, sertraline (Zoloft), paroxetine (Paxil), citalopram (Celexa), and escitalopram (Lexapro). All effectively treat major depression. In addition, one or more of the SSRIs has been shown effective in the treatment of dysthymic disorder, the depressive phase of bipolar disorder, premenstrual dysphoric disorder, panic disorder, social phobia, obsessive-compnlsive disorder, bnlimia nervosa, and binge-eating disorder. 

Fluvoxamine (Luvox). This is actually the oldest of the SSRIs. It is approved iu this couutry for the treatmeut of OCD but is also an effective treatment for major depression and many other anxiety disorders. It should be started at 50mg/day, and the effective dose range is from 100 to 300mg/day. Fluvoxamine is the only SSRI that must be takeu twice a day. The common side effects of fluvoxamine are comparable to other SSRIs. 

Uzunova V, Sheline Y, Davis JM, Rasmusson A, Uzunov DP, Costa E, Guidotti A (1998) Increase in the cerebrospinal fluid content of neurosteroids in patients with unipolar major depression who are receiving fluoxetine or fluvoxamine. Proc Natl Acad Sci USA 95 3239-3244... 

Holsboer F (2001) Stress, hypercortisolism and corticosteroid receptors in depression implications for therapy. J Affect Disord 62 77-91 Ito K, Yoshida K, Sato K, et al (2002) A variable number of tandem repeats in the serotonin transporter gene does not affect the antidepressant response to fluvoxamine. Psychiatry... 

Yu YW, Tsai SJ, Chen TJ, Lin CH, Hong CJ (2002) Association study of the serotonin transporter promoter polymorphism and symptomatology and antidepressant response in major depressive disorders. Mol Psychiatry 7 1115-1119 Zanardi R, Benedetti F, Di Bella D, Catalano M, Smeraldi E (2000) Efficacy of paroxetine in depression is influenced by a functional polymorphism within the promoter of the serotonin transporter gene. J Clin Psychopharmacol 20 105-107 Zanardi R, Serretti A, Rossini D, et al (2001) Factors affecting fluvoxamine antidepressant activity influence of pindolol and 5-HTTLPR in delusional and nondelusional depression. Biol Psychiatry 50 323-330... 

Initial pharmacogenetic studies of serotonin transporter gene (HTT) variants used case-control methods and have generated disparate results in different populations. Positive association of the promoter VNTR polymorphism (5-HTTLPR) with clinical response to fluvoxamine was seen in Italian patients with bipolar or unipolar delusional depression subjects with one or... 

Other SSRIs may be selected as an alternative to fluvoxamine in the event that fluvoxamine cannot be used. Sertraline is the first option because of efficacy for pediatric GAD (Rynn et ah, 2001) paroxetine is an option because of controlled treatment data for adolescent depression (Keller et ah, 2000) and OCD (see Chapter 39) and fluoxetine is an option because of controlled treatment data for pediatric depression (Em-slie et ah, 1997). Eorazepam is included as a short acting alternative to clonazepam. Nortriptyline, which is less anticholinergic and thus may be better tolerated, is included as an alternative to IMF... 

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. 

Apter, A., Ratzoni, G., King, R., Weizman, A., lancu, I., Binder, M., and Riddle, M. (1994) Fluvoxamine open-label treatment of adolescent inpatients with obsessive-compulsive disorder or depression. J Am Acad Child Adolesc Psychiatry 33 342-348. 

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