SSRIs Tricyclic antidepressants

Drugs that can increase carbamazepine serum levels include cimetidine, danazol, diltiazem, erythromycin, felbamate, clarithromycin, fluoxetine, isoniazid, niacinamide, propoxyphene, ketaconazole, itraconazole, verapamil, valproate, troleandomycin, loratadine, nicotinamide, tricyclic antidepressants, SSRIs, nefazodone, protease inhibitors. 

Long-acting benzodiazepines, tricyclic antidepressants, SSRIs, anti-psychotics... 

TCA, tricyclic antidepressant SSRI, selective serotonin reuptake inhibitor MAOI, monoamine oxidase inhibitor. 0, no effect +, + +, + + + indicate increasing effect. 

The major advantages of SSRIs over the tricyclic antidepressants are their less pronounced anticholinergic adverse effects and lack of severe cardiotoxicity. However, some studies have shown some degree of nervousness or agitation, sleep disturbances, gastrointestinal symptoms, and perhaps sexual adverse effects more commonly in patients treated with SSRIs than in those treated with tricyclic antidepressants. SSRIs may also be associated with an increased risk of suicide, particularly in children under 16 (9). 

Adverse interactions of lithium with tricyclic antidepressants, SSRIs, and monoamine oxidase inhibitors have been reviewed (581). In reviews of antidepressants and the serotonin syndrome, a possible contributory role has been suggested for lithium, based on case reports with tricyclic antidepressants, SSRIs, trazodone, and venlafax-ine (204,582). 

Although certain illnesses contribute to falls, medications have been shown to cause falls independent of other factors. The most commonly offending drugs are benzodiazepines because they have been shown to increase falls and hip fractures. An association between the dose (the higher the dose, the more likely the fall), duration of use, and type of benzodiazepine (e.g., long-acting medications) has also been reported. Other classes of medications that increase the risk of falls include tricyclic antidepressants, SSRIs, and opioid analgesics. 

Use of die MAOIs must be discontinued 2 weeks before the administration of die SSRIs. When the SSRIs are administered witii die tricyclic antidepressants, tiiere is an increased risk of toxic effects and an increased tiierapeutic effect. When sertraline is administered witii a MAOI, a potentially fatal reaction can occur. Sjymptoms of a serious reaction include hyper-tiiermia, rigidity, autonomic instability witii fluctuating vital signs and agitation, delirium, and coma Sertraline blood levels are increased when administered witii cimetidine. 

The main focus of pharmacoeconomic studies of antidepressants has inevitably fallen on comparisons between tricyclic antidepressants (TCAs) and the more expensive selective serotonin reuptake inhibitors (SSRIs). Few data are available for comparisons within the SSRIs or for newer antidepressants. 

Tricyclic antidepressants are not licensed for use in the anxiety disorders, so in theory the SSRIs should not be compared with them in cost-effectiveness terms. The SSRIs and venlafaxine are supplanting benzodiazepines as the latter s long-term problems become more appreciated. The SSRIs will take an increasing proportion of the market. However, in comparison with the overall costs of the anxiety disorders, this drug expenditure can be justified. Further cost-offset and cost-effectiveness studies will help hammer this point home. 

FIGURE 30-2. Pain algorithm. AED, antiepileptic drug APAP, acetaminophen NSAID, non-steroidal antiinflammatory drug SNRI, serotonin-norepinephrine reuptake inhibitor SSRI, selective serotonin reuptake inhibitor TCA, tricyclic antidepressant. 

MAOI, monoamine oxidase inhibitor SSRI, selective serotonin reuptake inhibitor TCA, tricyclic antidepressant. 

SSRIs, selective serotonin reuptake inhibitors TCAs, tricyclic antidepressants NSAIDs, non-steroidal anti-inflammatory drugs. 

The tricyclic antidepressant clomipramine also has been studied for PMDD. In placebo-controlled trials, both continuous daily dosing and luteal phase administration proved effective.17 Compared with the SSRIs, however, clomipramine has a less desirable side-effect profile with low tolerability. 

CYP2C19 is another example of the existence of both cross-ethnic and inter-individual variations in drug metabolism. This enzyme is involved in the metabolism of many psychotropics such as diazepam and tertiary tricyclic antidepressants, as well as one of the selective serotonin re-uptake inhibitors (SSRIs), citalopram. Using S-mephenytoin as the probe, previous studies showed that up to 20% of East Asians (Chinese, Japanese, and Koreans) are PMs, when only 3-5%... 

At first, Sapirstein and I found the equivalence between antidepressants and other drugs puzzling, to say the least. Why should drugs that are not antidepressants be as effective as antidepressants in treating depression To answer this question, we asked another. What do all these diverse drugs have in common that they do not share with inert placebos What do SSRIs have in common with the older tricyclic antidepressants, with other less common antidepressants, and even with tranquillizers, depressants and thyroid medication The only common factor that we were able to note was that they all produce easily noticeable side effects - the one thing that was lacking in Merck s new treatment for depression. Placebos can also produce side effects, but they do so to a much lesser extent than active medication. Clinical trials show that whereas the therapeutic benefits of antidepressants are relatively small when compared to placebos, the difference in side effects is substantial.7... 

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... 

In many clinical trials a positive control of a clinically established drug is often used for comparison purposes for example, a novel selective serotonin reuptake inhibitor (SSRI), may be compared with a more established tricyclic antidepressant, such as imipramine. The aim is to see whether the new SSRI is more efficacious or has fewer adverse side effects than the more established tricyclic (Chapter 12). In many such comparisons the new and older treatments are equally efficacious at relieving depression, but the newer drugs display fewer side effects this means that they are better tolerated by patients, so that they are more willing to continue taking the tablets. The high rates of compliance also mean that, in overall terms, newer drugs with fewer side effects tend to be more efficacious. 

Until the introduction of selective serotonin reuptake inhibitors (SSRIs) in the 1980s, tricyclic antidepressants were the most widely used drugs. The therapeutic effect of amitriptyline and imipramine are related to their ability to inhibit the presynaptic reuptake of both NA and 5-HT. They are referred to as non-selective reuptake inhibitors, whereas many of the other tricyclics are more selective thus, clomipramine is a selective reuptake inhibitor for 5-HT and desipramine and nortriptyline are selective... 

In addition to this serious diet-drug interaction, irreversible MAOIs also potentiate the effects of sympathomimetic drugs like ephedrine found in over-the-counter cold remedies and recreational stimulants like amphetamine. The MAOIs also interact with drugs that increase synaptic concentrations of 5-HT, such as the tricyclic antidepressant clomipramine and the herbal SSRI antidepressant St John s wort (Hypericum spp.). The resulting serotonin syndrome is characterised by hyperthermia and muscle rigidity. While devoid of these side effects the reversible MAO-A inhibitor moclobemide has yet to establish itself as a first-line alternative to the SSRIs. 

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