SSRIs Smoking

There is a decreased effectiveness of fluoxetine in patients who smoke cigarettes during administration of die drug. Fluoxetine is not administered witii lithium because this combination can increase lithium levels. The SSRIs are not administered witii herbal preparations containing St. Jbhn s wort because tiiere is an increased risk for severe reactions. 

Several other clinically available pharmacological agents have been tested for their potential to facilitate smoking cessation, although they are not approved by the FDA for this purpose. For example, tricyclic antidepressants, which inhibit reuptake of noradrenaline and 5-HT, promote smoking cessation in conjunction with behavioral treatment in some individuals.107 However, these medications are limited because of their significant side effects. 5-HT-selective reuptake inhibitors (SSRIs) are believed to be a safer class of antidepressants but have not demonstrated effectiveness in smoking cessation.108... 

Factors reported to influence TCA plasma concentrations include disease states (e.g., renal or hepatic dysfunction), genetics, age, cigarette smoking, and concurrent drug administration. Similarly, hepatic impairment, renal impairment, and age have been reported to influence the pharmacokinetics of SSRIs. 

After more than a decade of use, bupropion (24) is considered a safe and effective antidepressant, suitable for use as first-line treatment. In addition, it is approved for smoking cessation and seasonal affective disorder. It is also prescribed off-label to treat the sexual dysfunction induced by SSRIs. Bupropion is often referred to as an atypical antidepressant and has much lower affinity for the monoamine transporters compared with other monoamine reuptake inhibitors. The mechanism of action of bupropion is still uncertain but may be related to inhibition of dopamine and norepinephrine reuptake transporters as a result of active metabolites [71,72]. In a recently reported clinical trial, bupropion extended release (XL) had a sexual tolerability profile significantly better than that of escitalopram with similar re-... 

The use of antidepressants outside the treatment of MDD tends to require specific agents. For example, the TCAs and SNRIs appear to be useful in the treatment of pain conditions, but other antidepressant classes appear to be far less effective. SSRIs and the highly serotonergic TCA, clomipramine, are effective in the treatment of OCD, but noradrenergic antidepressants have not proved to be as helpful for this condition. Bupropion and nortriptyline have usefulness in the treatment of smoking cessation, but SSRIs have not been proven useful. Thus, outside the treatment of depression, the choice of antidepressant is primarily dependent on the known benefit of a particular antidepressant or class for a particular indication. 

Amfebutamone is used to encourage smoking cessation and in some countries as an antidepressant. In some respects its adverse effects profile is similar to that of the SSRIs insomnia, agitation, tremor, and nausea are most often reported. 

SSRIs in particular have come to be used increasingly in a variety of conditions other than major depression. Table 8.4 summarizes the uses for which SSRIs have been approved, based on the finding of significant beneficial effects in controlled clinical trials. In addition, agents in this class in controlled trials have shown usefulness in premenstrual dysphoria, borderline personality disorder, obesity, smoking cessation, and alcoholism (17). 

Cimetidine, fluoroquinolone antibiotics such as ciprofloxacin and the selective serotonin-reuptake inhibitor (SSRI) fluvoxamine inhibit the metabolism of theophylline, whereas, the its metabolism can be induced by smoking or by the ingestion of char-broiled meats. 

What conclusions can be drawn from these four studies First, the reports of Diav-Citrin et al [19 ] and Pedersen et al [21 ] confirm prior reports of increased rates of cardiovascular anomalies with SSRIs, suggesting that this is a class effect rather than specific to paroxetine, as some previous studies had suggested. The report of Diav-Citrin highlights the importance of accounting for other potential confounders, such as smoking and maternal age, while that of Pedersen et al suggests that the main anomaly is that of septal heart defects and that the use of multiple SSRIs may further increase risk. 

---