Antidepressant drugs antidepressants efficacy

Chinese depressed patients appeared to require lower dosages, with consequently lower plasma concentrations of sertraline compared to Caucasian patients to achieve clinical efficacy (Ng et al, 2006). Again, this finding has supported the fact that Asian patients, especially Chinese, need lower doses of antidepressant drugs than their Western counterparts. 

Lithium is effective for acute mania, but it may require 6 to 8 weeks to show antidepressant efficacy. It may be more effective for elated mania and less effective for mania with psychotic features, mixed episodes, rapid cycling, and when alcohol and drug abuse is present. Maintenance therapy is more effective in patients with fewer episodes, good functioning between episodes, and when there is a family history of good response to lithium. It produces a prophylactic response in up to two-thirds of patients and reduces suicide risk by eight- to 10-fold. 

Clomipramine (Anafranil) also a member of the tricyclic family, possesses similar pharmacology and antidepressant efficacy. This agent, however, has Food and Drug (FDA) approval only for use in the treatment of obsessive-compulsive disorder and is not included in this discussion of antidepressant drugs. 

Many psychotropic drugs from various classes other than antidepressants have been shown over the years also to suppress REM sleep, but they do not have any antidepressant efficacy (Kales 1995). A review, however, indicated that, compared with other REM suppressant drugs, antidepressants produce a suppression of REM sleep that is larger, more persistent, and followed more frequently by REM rebound on drug discontinuation (G. W. Vogel et al. 1990). Thus, differences across drug classes indeed make antidepressants unique, with their REM suppressant effect paralleling only that of the arousal-induced REM sleep deprivation. 

It has been assumed that the REM suppressing properties are a prerequisite for the antidepressant efficacy of a drug (G. W. Vogel 1975, 1983). It is now clear that this position was an oversimplification (Montero and Berger 1995). Actually, G. W. Vogel et al. (1990) admitted that only a correlation exists between antidepressant efficacy and drug effect on REM sleep, and, of... 

Preskorn SH, Fast GA. Therapeutic drug monitoring for antidepressants efficacy, safety and cost effectiveness. J Clin Psychiatry 1991 52(suppl 6) 23-33. 

Mianserin and its analogue, mirtazapine (i.e., 6-azo-mianserin), are tetracyclic compounds and differ from other antidepressants in terms of the putative mechanism responsible for their antidepressant efficacy (171). Mianserin is the older drug and is marketed in several countries around the world but not in the United States. 

Interest in drugs that inhibit monoamine oxidase has been spurred, not only by controlled studies that document their antidepressant efficacy, but also by the demonstration of their benefit in the treatment of the following ... 

As mentioned earlier, for certain patients there may be no class of antidepressants with better efficacy than the TCAs. For this reason alone, these medications remain a valuable part of the antidepressant armamentarium. When the dose of a TCA is adjusted based on clinic assessment of response, a TCA will produce at least a partial response in 60% to 70% of depressed patients and a full remission in 20% to 40%. When the dose is adjusted using therapeutic drug monitoring (TDM), the full remission rate may be higher. 

Although studies have been done with virtually all of the SSRIs attempting to correlate antidepressant efficacy with plasma drug levels, they have consistently failed to find a relationship (121,342, 343, 344, 345, 346, 347 and 348). However, a relationship has been found between the plasma levels of each SSRI achieved on the lowest, usually effective dose and the ability to inhibit approximately 70% to 80% of serotonin uptake ( 25). Thus, patients who have SSRI plasma levels below this threshold have probably not had an optimal trial of the SSRI as a result of rapid clearance, inadequate dose, or noncompliance. 

Whereas tertiary amine TCAs are more potent than secondary amine TCAs in terms of sites of action mediating adverse effects, they are less potent than secondary amine TCAs in terms of antidepressant efficacy based on the results of the plasma drug level studies reviewed earlier in this chapter. That fact further increases the safety and tolerability of secondary amine versus tertiary amine TCAs (411). Nevertheless, secondary amine TCAs are still toxic when taken in overdose, and this issue must always be considered when applying treatment in a patient who poses a substantial suicide risk. 

The overall efficacy of ECT was 78%, which is significantly superior to that of tricyclic antidepressants, whose overall efficacy was 64%, as well as to placebo, simulated ECT, and the monoamine oxidase inhibitors, whose overall response rates ranged from 28% to 38%. This difference was particularly striking because many patients in the ECT-treated groups had failed previous drug trials. The adequacy of some of these, however, was questionable. Furthermore, in contrast to other reports, our analysis did not find a significant difference favoring BILAT over UND ECT (i.e., only a 7% overall difference). 

This observation is a rare phenomenon in pharmacology. Meta-analyses of studies comparing various standard antidepressants for major depressive disorder reveal that all are equally efficacious (see Chapter 7). Similarly, meta-analyses of studies comparing antipsychotics find all equally efficacious for psychotic disorders (see Chapter 5). It is unusual to find a subclass of drugs more efficacious than others in the same class. Hence, if some antidepressants are clearly more effective than other antidepressants in OCD, it is truly noteworthy. 

Lithium carbonate and lithium citrate are the most commonly used compounds. Lithium has effects on cation transport, on individual neurotransmitters (including 5-HT) and on intracellular second messenger systems. Which of these is key to its therapeutic efficacy is not entirely clear but, as for the antidepressant drugs, the net effects seem to be to enhance serotonin function and to stabilise the noradrenergic system. Once lithium treatment is established it is very important that it is not suddenly stopped as this may result in rebound hypomania. 

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. 

It is interesting to note that despite the very widespread use and the generally accepted efficacy of antidepressants in pain therapy, at present not all antidepressant drugs are formally approved for the treatment of pain. Thus, the widespread use of these drugs is, to some extent, off-label, and there does not seem to be much effort in the pharmaceutical industry to market antidepressants explicitley as analgesic drugs. 

Desipramine is a tricyclic antidepressant that has been tested in several double-blind trials among cocaine addicts. Like cocaine, desipramine inhibits monoamine neurotransmitter reuptake, but its principal effects are on norepinephrine reuptake. It was hypothesized that desipramine could relieve some of the withdrawal symptoms of cocaine dependence and reduce the desire for cocaine during the vulnerable period following cessation of cocaine. This drug showed efficacy early in the epidemic in a group of patients who were primarily white collar intranasal cocaine users. The majority of subsequent studies of desipramine-using, more severely ill cocaine addicts have been negative. 

Noncompliance is an important cause of lack of response to drugs. Patients should be warned also that noticeable improvement may be slow, perhaps taking 3 weeks or more. Inability to tolerate adverse effects and discouragement with treatment are two major causes for noncompliance and for failure of antidepressants to show efficacy. 

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