Antidepressant Pharmacotherapy

A modulatory, predominantly inhibitory effect of serotonin reuptake inhibiting drugs on activation of proinflammatory immune parameters was demonstrated in animal experiments (Bengtsson et al., 1992 Song and Leonard, 1994 Zhu et al., 1994). 

Several antidepressants seem to be able to induce a shift from a type-1 to a type-2, from a proinflammatory to an antiinflammatory immune response, since the ability of different antidepressants (sertraline, clomipramine, trazodone) to reduce the IFN-y/IL-10 ratio significantly was shown in vitro. These drugs reduced the IFN-y production significantly, while sertraline and clomipramine additionally raised the IL-10 production (Maes et al., 1999). Regarding other in-vitro studies, a significantly reduced production of IFN-y, IL-2, and sIL-2R was found after antidepressant treatment compared to pretreatment values (Seidel et al., 1995, b). A down-regulation 

Regarding serum levels, several researchers observed a reduction of IL-6 during treatment with the serotonin reuptake inhibitor fluoxetine (Sluzewska et al., 1995). A decrease of IL-6 serum levels during therapy with different antidepressants has been observed by other researchers (Frommberger et al., 1997). On the other hand, other groups did not find any effect of certain antidepressants on serum levels of different cytokines (Maes et al., 1995a, 1997). 

Since IL-6 stimulates Prostaglandin (PGEj) and antidepressants inhibit the IL-6 production, an inhibiting action of antidepressants on PGEj would be expected, too (Poliak and Yirmiya, 2002). Over twenty years ago it was suggested that antidepressants inhibit PGEj (Mtabaji et al., 1977). A recent in-vitro study showed that both tricyclic antidepressants and selective serotonin inhibitors attenuated cytokine-induced PGEj and nitric oxide production by inflammatory cells (Yaron et al., 1999). 

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It is essential that research to assess the cost-effectiveness of antidepressant pharmacotherapy continues and that better pharmacoeconomic research methods evolve. Naturalistic studies may be used to observe how antidepressant dmgs petform in practice. 

Sclar DA, Robison LM, Skaer TL et al (1994). Antidepressant pharmacotherapy economic outcomes in a Health Maintenance Organisation. Clin 16, 715—30. 

SkaerTL, Sclar DA, Robison LM, et al (1996). Antidepressant pharmacotherapy effect on women s resource utilization within a health maintenance organization. Appl Ther 1, 45-52. 

Stewart A (1994). Antidepressant pharmacotherapy cost comparison of SSRIs and TCAs. Br J... 

Tsolaki M, Fountoulakis KN, Nakopoulou E and Kazis A (2000). The effect of antidepressant pharmacotherapy with venlafaxine in geriatric depression. International Journal of Geriatric Psychopharmacology, 2, 83-85. 

Pteskotn, S.H., and Othmet, S.C. (1984) Evaluation of bupropion hydrochloride the fitst of a new class of atypical antidepressants. Pharmacotherapy 4 20-34. 

Perhaps the greatest research need in antidepressant pharmacotherapy is what to do when the first antidepressant trial fails to produce response. Indeed, in clinical trials, 35% to 40% of patients do not achieve a 50% reduction in their symptoms on any single antidepressant and the majority do not have a full remission. Thus, this discussion is relevant to the majority of patients with major depression. 

An important aspect of antidepressant pharmacotherapy is selection based on the adverse effect profile of a specific medication, because most antidepressants are comparable in terms of efficacy. One of the major accomplishments of modern antidepressant development has been to improve the adverse effect profile of newer agents in comparison with TCAs and MAOIs without compromising efficacy (1). That has been accomplished by developing chemicals that retain the ability to affect sites of action that appear to be capable of mediating antidepressant efficacy (e.g., the serotonin uptake pump), but avoid effects on unnecessary sites of action (e.g., ACh receptor, fast sodium channels). This approach has led to both better tolerated and safer medications. Table 7-23 lists the common potential adverse affects of a number of antidepressants, as well as their relative severity. 

Mann J, Kapur S. The emergence of suicidal ideation and behavior during antidepressant pharmacotherapy. Arch Gen Psychiatry 1991 48 1027-1033. 

Montgomery SA. Venlafaxine a new dimension in antidepressant pharmacotherapy. J Clin Psychiatry... 

Iwamoto ET, Marion L (1993) Characterization of the antinociception produced by intrathecally administered muscarinic agonists in rats. J Phtirmacol Exp Ther 266 329-338 Jackson KC, St Onge EL (2003) Antidepressant pharmacotherapy considerations for the pain clinician. Pain Pract 3 135-143... 

Chromium can potentiate antidepressant pharmacotherapy for manic-depressive disorder. In five patients taking sertraline, supplementation with chromium picolinate and chromium polynicotinate led to enhanced remission of dysthymic symptoms (23). 

McLeod MN, Gaynes BN, Golden RN. Chromium potentiation of antidepressant pharmacotherapy for dysthymic disorder in 5 patients. J Clin Psychiatry 1999 60(4) 237 0. 

Hersom K, Neary MP, Levaux HP, et al. Isotretinoin and antidepressant pharmacotherapy a prescription sequence symmetry analysis. J Am Acad Dermatol 2003 49 424-432. 

Trigclic Antidepressants. Imipramine (38) was introduced in the late 1950s as one of the first pharmacotherapies for depression. At that time, chlorproma2ine [50-53-3] was the first effective antipsychotic treatment to be discovered. Researchers looked for similar chemical stmctures and imipramine was found to be effective in the symptomatic treatment of depression. Over the years, other congeners, such as desipramine (39), amitriptyline (40), and dothiepin (41), were synthesized and shown to be clinically efficacious antidepressant dmgs (121). These substances, known under the general mbric of tricycHc antidepressants, share a basic chemical stmcture comprising... 

Ciraulo DA, Jaffe JH Tricyclic antidepressants in the treatment of depression associated with alcoholism. Clin Psychopharmacol 1 146—150, 1981 Ciraulo DA, Nace E Benzodiazepine treatment of anxiety or insomnia in substance abuse patients. Am J Addict 9 276—284, 2000 Ciraulo DA, Barnhill JG, Jaffe JH, et al Intravenous pharmacokinetics of 2-hydroxy-imipramine in alcoholics and normal controls. J StudAlcohol 51 366-372, 1990 Ciraulo DA, Knapp CM, LoCastro J, et al A benzodiazepine mood effect scale reliability and validity determined for alcohol-dependent subjects and adults with a parental history of alcoholism. Am J Drug Alcohol Abuse 27 339—347, 2001 Collins MA Tetrahydropapaveroline in Parkinson s disease and alcoholism a look back in honor of Merton Sandler. Neurotoxicology 25 117-120, 2004 COMBINE Study Research Group Testing combined pharmacotherapies and behavioral interventions in alcohol dependence rationale and methods. Alcohol Clin Exp Res 27 1107-1122, 2003a... 

More than 40 medications have been investigated but none have shown consistent efficacy for primary cocaine or amphetamine dependence. These medications include dopaminergic agonists, antidepressants, and more recently disulfiram, selegiline, and a cocaine vaccine (see Table 5—2 for summary). Studies have been relatively brief and have focused on abstinence initiation rather than on relapse prevention, but even these modest treatment goals have not been attained. The focus in the discussion that follows is on pharmacotherapies for cocaine dependence, because very few clinical trials have been completed with amphetamine-dependent patients. Furthermore, none of the studies of amphetamine dependence have shown results different from those described for cocaine dependence (Rawson et al. 2002b Srisurapanont et al. 2001). 

Various forms of psychotherapy are regarded as effective interventions in mild to moderate depression, but studies comparing the economics of psychotherapy and pharmacotherapy are few (Rosenbaum and Hylan, 1999). One study found that the total health-care costs for patients who received psychotherapy were no different from those for patients who received an antidepressant. However, no efficacy measure was used (Edgell and Hylan, 1997). A randomized, prospective study which evaluated the treatment of depression with nortriptyline, interpersonal therapy or treatment as usual, with outcomes expressed in quality-adjusted life years, found that nortriptyline but not interpersonal therapy was a cost-effective alternative to treatment as usual (Lave et al, 1998). 

The proposed mechanism of ADHD pharmacotherapy is to modulate neurotransmitters in order to improve academic and social functioning. Pharmacologic therapy can be divided into two categories stimulants and non-stimulants. Stimulant medications include methylphenidate, dexmethylphenidate, amphetamine salts, and dextroamphetamine, whereas non-stimulant medications include atomoxetine, tricyclic antidepressants (e.g., imipramine), clonidine, guanfacine, and bupropion. 

Research in psychopharmacology has shown that ethnicity must be considered in psychiatry as well (Lawson, 1986 Pi 8c Simpson, 2005). Early clinical trials with antipsychotic and antidepressant medications showed that ethnic minorities may respond when given the same doses as Caucasians, and may have more side effects (Lawson, 1986 Lawson, 1990). However, dosing cannot be used as a measure of appropriate pharmacotherapy because an extensive literature has shown that African Americans often receive higher doses of antipsychotics despite evidence of more side effects. 

Table 68-14 shows antidepressants used in the treatment of PTSD, and Fig. 68-4 shows an algorithm for the pharmacotherapy of PTSD. 

There are numerous antidepressant medications on the market (table 7.1). Following development of monoamine oxidase (MAO) inhibitors were tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), and several atypical antidepressants (Baldessarini 1996). Successive generations of antidepressants have not necessarily become more effective in treating depression, but rather offer more favorable side-effect profiles—a crucial factor in effective clinical pharmacotherapy. An effective medication is not useful if its side effects are intolerable. 

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