Selective serotonin reuptake inhibitors limits

Patients seen for flashbacks are treated with oral diazepam (15—30 mg/day for adults) if symptoms of anxiety are severe (Rumack 1987). Neuroleptics, especially haloperidol, have been implicated in a transient increase in visual flashbacks and are not recommended (Moskowitz 1971 Strassman 1984). Risperidone and selective serotonin reuptake inhibitors may also worsen symptoms of hallucinogen persisting perception disorder (Halpern and Pope 2003). The patient needs assurance of the self-limiting nature of the phenomenon and its decreasing frequency of reoccurrence with time. The patient should be reminded that any future use of hallucinogens or marijuana may precipitate similar symptoms (Strassman 1984). 

Alternatives to estrogen for hot flushes are shown in Table 31-6. Progesterone alone may be an option in women with a history of breast cancer or venous thrombosis, but side effects limit their use. For women with contraindications to hormone therapy, selective serotonin reuptake inhibitors and venlafaxine are considered by some to be first-line therapy, but efficacy of venlafaxine beyond 12 weeks has not been shown. 

The traditional scheme is complicated by the fact that some antidepressants exhibit characteristics of more than one class. For example, clomipramine, a tricyclic antidepressant (TCA) with side effects and toxicity similar to other TCAs, works more like the selective serotonin reuptake inhibitors (SSRls). Similarly, venlafaxine and duloxetine, which are usually grouped with the atypical antidepressants, have a side effect and safety profile comparable to the SSRls. Although a classihcation system based on mechanism of action offers some advantage (see Table 3.7), even this scheme is limited by the fact that antidepressants that work in the same way may have widely divergent side effect and safety profiles. In the following discussion, the traditional classification system is adopted. Although fraught with problems and inconsistencies. 

Specific factors to consider are both psychiatric and physical contraindications. For example, bupropion is contraindicated in a depressed patient with a history of seizures due to the increased risk of recurrence while on this agent. Conversely, it may be an appropriate choice for a bipolar disorder with intermittent depressive episodes that is otherwise under good control with standard mood stabilizers. This consideration is based on the limited data suggesting that bupropion is less likely to induce a manic switch in comparison with standard heterocyclic antidepressants. Another example is the avoidance of benzodiazepines for the treatment of panic disorder in a patient with a history of alcohol or sedative-hypnotic abuse due to the increased risk of misuse or dependency. In this situation, a selective serotonin reuptake inhibitor (SSRI) may be more appropriate. 

The depressive phase of manic-depressive disorder often requires concurrent use of an antidepressant drug (see Chapter 30). Tricyclic antidepressant agents have been linked to precipitation of mania, with more rapid cycling of mood swings, although most patients do not show this effect. Selective serotonin reuptake inhibitors are less likely to induce mania but may have limited efficacy. Bupropion has shown some promise but—like tricyclic antidepressants—may induce mania at higher doses. As shown in recent controlled trials, the anticonvulsant lamotrigine is effective for many patients with bipolar depression. For some patients, however, one of the older monoamine oxidase inhibitors may be the antidepressant of choice. Quetiapine and the combination of olanzapine and fluoxetine has been approved for use in bipolar depression. 

SSRI selective serotonin reuptake inhibitor ULN upper limit of normal... 

Fewer adverse effects were reported among moclobemide-treated patients compared with selective serotonin reuptake inhibitor (SSRI)-treated patients. Since moclobemide does not induce orthostatic hypotension, does not possess anticholinergic properties, and is not cardiotoxic, it is very well suited among the MAOIs for the treatment of depression. Moclobemide has limited potential to elicit a hypertensive crisis, because the pressor effect of tyramine from food is only marginally potentiated compared with tranylcypromine. The pressor effect of tyramine is normalized within 3 days of cessation of treatment with moclobemide. The combination of SSRIs and moclobemide has good efficacy in cases of refractory depression, but there is controversy as to whether toxic side-effects such as serotonin syndrome can result from this combination. Currently, more studies are needed before this combination can be recommended. Acute overdose with MAOIs causes agitation, hallucinations, hyperpyrexia, hyperreflexia, convulsions, and death. The most dangerous MAOIs in overdose are the irreversible non-selective MAOIs. T2s-27... 

Another example of chiral switching is that of the selective serotonin reuptake inhibitor (SSRI) antidepressant Celexa, which was introduced to the market in 1998 by Forest Laboratories. Celexa is a racemic mixture of (i )-citalopram oxalate and (5)-citalopram oxalate. While orrly the (S) enantiomer has therapeutic antidepressant properties, both enantiomers contribute to the side effects of the drug and therefore limit effectiveness and patient tolerance. In 2002, the FDA approved Lexapro, a new antidepressant derived from Celexa but from which the therapeutically ineffective (R) enantiomer has been removed. The benefits of isolating the active isomer include smaller required dosages, reduced side effects, and a faster and better patient response to the drag. 

The modest improvements achieved in selectivity with respect to serotonin reuptake inhibition may also have been achieved with an isoenzyme system. Moclobemide, which was introduced in Sweden, reversibly inhibits monoamine oxidase A (RIMA). It is likely that this eliminates the severe hypertensive drug and food interactions that so severely limit the usefulness of the very effective earlier MAO inhibitors, since tyramine is now metabolized. An additional benefit of such agents may be a lack of cholinergic and cardiovascular effects. 

This chapter describes two microbore LC-based methods for measurement of monoamine neurotransmitters in rat brain dialysates a method for the determination of the catecholamines (CA) noradrenaline (NAD), adrenaline (AD), and dopamine (DA) and a method for the determination of the indoleamine serotonin (5HT) and its major metabolite 5-hydroxyindoleacetic acid (SHIAA) (3). For all compounds, a limit of detection of 1 pmol or less (in an injected volume of 10 pL) can be achieved. Basal serotonin can be measured in microdialysates without including a reuptake inhibitor in the microdialysis perfusion fluid. Both of these systems are routinely used in the authors laboratory for the analysis of dialysates from striatum, hippocampus, and substantia nigra. Both methods are selective, robust, and can be automated. 

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