Selective serotonin reuptake inhibitor metabolic

SSRI = Selective serotonin reuptake inhibitor NSAID = Nonsteroidal anti-inflammatory drug CYP = cytochrome P-450 NAT2 = N-acetyl transferase type 2 J = Japanese C = Chinese A = African American. Poor metabolizers are not always at increased risk of ADR. 

Naranjo, C.A., Sproule, B.A. and Knoke, D.M. (1999) Metabolic interactions of central nervous system medications and selective serotonin reuptake inhibitors. International Clinical Psychopharmacology, 14 (Suppl. 2), S35-S47. 

Serendipity has played a major role in the discovery of most classes of psychotropic drugs. For example, the observation that the first antidepressants, the tricyclic antidepressants and the monoamine oxidase inhibitors, impeded the reuptake of biogenic amines into brain slices, or inhibited their metabolism, following their acute administration to rats, provided the experimenter with a mechanism that could be easily investigated in vitro. Such methods led to the development of numerous antidepressants that differed in their potency, and to some extent in their side effects (for example, the selective serotonin reuptake inhibitors) but did little to further the development of novel antidepressants showing greater therapeutic efficacy. The accidental discovery of atypical antidepressants such as mianserin led to the broadening of the basis of the animal models... 

Preskorn, S.H. (1997) Clinically relevant pharmacology of selective serotonin reuptake inhibitors. An overview with emphasis on pharmacokinetics and effects on oxidative drug metabolism. Clin Pharmacokinet 32 1-21. 

Although tricyclics continue to be used today to treat childhood depression (Zito et ah, 2000), the use in children with ADHD has decreased, most likely because of its association with the sudden deaths of five children (Biederman, 1991). Furthermore, the Physician s Desk Reference (PDR) warns that MPH may inhibit the metabolism of tricyclics, but no such warning exists for DEX or (AMP). Due to the concern that children on this combination of medications are prone to develop more side effects, it is not a recommended form of treatment. Instead, MPH combined with a selective serotonin reuptake inhibitor is preferable for treating a child with ADHD and comorbid depression. 

It is of note that Hypericum, often described as the natural Prozac, has the opposite effect of fluoxetine— and selective serotonin reuptake inhibitors (SSRIs) in general—on the CYP system. Fluoxetine inhibits several CYP isoenzymes, potentially resulting in increased blood levels of drugs metabolized through this pathway (See Chapter 22). 

Selective serotonin reuptake inhibitors. Currently available selective serotonin reuptake inhibitors (SSRIs) include fluoxetine, paroxetine, sertraline, fluvoxamine, and citalopram. At present, expert opinion does not support the usefulness of these serotonergic compounds in the treatment of core ADHD symptoms (National Institute of Mental Health, 1996). Nevertheless, because of the high rates of comorbidity in ADHD, these compounds are frequently combined with effective anti-ADHD agents (see Combined Pharmacotherapy, below). Since many psychotropics are metabolized by the cytochrome P450 system (Nemeroff et ah, 1996), which in turn can be inhibited by the SSRIs, caution should be exercised when combining agents, such as the TCAs, with SSRIs. 

Selective serotonin reuptake inhibitors (SSRIs) [P] Fluoxetine and paroxetine inhibit CYP2D6 and decrease metabolism of antidepressants metabolized by this enzyme (eg, desipramine). Citalopram, sertraline, and fluvoxamine are only weak inhibitors of CYP2D6, but fluvoxamine inhibits CYP1A2 and CYP3A4 and thus can inhibit the metabolism of antidepressants metabolized by these enzymes. 

Selective serotonin reuptake inhibitors (SSRIs) [NE] Fluoxetine and fluvoxamine decrease carbamazepine metabolism. 

Belpaire FM, Wijnant P, Temmerman A, et al. The oxidative metabolism of metoprolol in human liver microsomes-inhibition by the selective serotonin reuptake inhibitors. Eur J Clin Pharmacol 1998 54 261-264. 

Baker GB, Fang J, Sinha S, et al. Metabolic drug interactions with selective serotonin reuptake inhibitor (SSRI) antidepressants. Neurosci Biobehav Rev 1998 22 325-333. 

Selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine, interact with drugs including clarithromycin, warfarin, phenelzine, benzotropine, chlorpromazine, diazepam, and cyproheptadine. Cigarette smokers metabolize SSRIs faster. 

Antidepressants generally fall into one of three categories (1) tricyclic antidepressants (TCAs), which are so named because of their three-ring chemical structure (2) selective serotonin reuptake inhibitors (SSRIs), which block only the reabsorption of serotonin and not of norepinephrine and (3) monoamine oxidase (MAO) inhibitors, which inhibit the metabolic breakdown of norepinephrine and/or serotonin. 

The transporter removes 5-HT after its release into the synaptic cleft and returns it to the presynaptic terminal, where it is metabolized by monoaminoxidases or stored in secretory vesicles and results in the termination of postsynaptic serotonergic effects (42). 5-HTT is the target of the selective serotonin reuptake inhibitors (SSRIs) that have been shown to be effective in certain anxiety disorders and depression (43). 

Von Moltke LL, Greenblatt DJ, Duan SX, et al. Inhibition of terfenadine metabolism in vitro by azole antifungal agents and by selective serotonin reuptake inhibitor antidepressants Relations to pharmacokinetic interactions in vivo. / Clin Psychopharmacol. 1996 16 104-112. 

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