Selective serotonin reuptake inhibitors pharmacology

Hiemke C. and S. Harther (2000). Pharmacokinetics of selective serotonin reuptake inhibitors. Pharmacology and Therapeutics 85 11-28. 

There is, however, a unique risk in the bipolar form that antidepressant treatment may trigger a switch into mania. This may occur either as the natural outcome of recovery from depression or as a pharmacological effect of the drug. Particular antidepressants (the selective serotonin reuptake inhibitors) seem less liable to induce the switch into mania than other antidepressants or electroconvulsive therapy. Treatment for mania consists initially of antipsychotic medication, for instance the widely used haloperidol, often combined with other less specific sedative medication such as the benzodiazepines (lorazepam intramuscularly or diazepam orally). The manic state will usually begin to subside within hours and this improvement develops further over the next 2 weeks. If the patient remains disturbed with manic symptoms, additional treatment with a mood stabilizer may help. 

When treating anxiety one should of course first treat any reversible medical condition. When pharmacological treatment is necessary SSRI is most often drug of choice. Selective serotonin reuptake inhibitors are both effective and safe. Benzodiazepines that have been widely used are drugs with a relative high risk of adverse effects (see Chapter 4). Risks for dependence and abuse must always be considered for benzodiazepines. 

Preskorn S. (1997). Clinically relevant pharmacology of selective serotonin reuptake inhibitors. Clinical Pharmacokinetics. 32 1-21. 

Leonard, H.L., March, J., Rickler, K.C., and Allen, A.J. (1997) Pharmacology of the selective serotonin reuptake inhibitors in children and adolescents. / Am Acad Child Adolesc Psychiatry 36 725-736. 

FIGURE 43.1 Pharmacologic treatment algorithm for full syndrome pediatric PTSD. Based on a snythesis of consensus data and clinical reports in the adult and child literature. The author hers no responsibility for the use of this guideline by third parties. SSRI, selective serotonin reuptake inhibitor NEE, nefaza-done SIB, self injurious behavior VLF, venlafaxine VPA, valproic acid. 

Hirano, Kazufumi, Ryohei Kimura, Yumi Sugimoto, Jun Yamada, Shinya Uchida, Yasuhiro Kato, Hisakuni Hashimoto, and Shizuo Yamada. Relationship Between Brain Serotonin Transporter Binding, Plasma Concentration and Behavioural Effect of Selective Serotonin Reuptake Inhibitors. British Journal of Pharmacology 144 (2005) 695-702. The researchers show that SSRIs begin to act on serotonin transporters within hours. 

The prevalence of anxiety disorders has spurred the search for pharmacological ways to treat these pathologies. To date, doctors have found that drugs from two broad classes—the benzodiazepines and selective serotonin reuptake inhibitors. 

In this chapter, we review the pharmacology of several selective serotonin reuptake inhibitors [SSRIs] and other drugs that act on the serotonergic system. That these developments have enhanced safety and tolerability is now beyond dispute, but it is also clear that these agents are no more effective than the old-style tricyclic antidepressants [TCAs]. [For a comprehensive discussion of serotonergic medication, see Montgomery, Chapter 12, in this volume.] Here, several compounds are discussed in detail. 

Hyttel J Pharmacological characterization of selective serotonin reuptake inhibitors (SSRls). Int Clin Psychopharmacol 9 (suppl l) 19-26, 1994 Hytell J, Larsen J-J Serotonin-selective antidepressants. Acta Pharmacol Toxicol 56 (suppl 1) 146-153, 1985... 

Preskorn SH. The adverse effect profiles of the selective serotonin reuptake inhibitors relationship to in vitro pharmacology. J Psychiatr Pract 2000 6 153-157. 

The similar pharmacological profile of selective serotonin reuptake inhibitors and St. John s wort would suggest the potential of a pharmacodynamic interaction due to an additive effect. A case of concurrent use of sertraline and St. John s wort, resulting in mania, was reported for a patient with a history of depression who was prescribed sertraline and who also took St. John s wort against medical advice (58). A similar potentiation of serotonergic effect was reported by Gordon (49). 

Nemeroff CB The clinical pharmacology and use of paroxetine, a new selective serotonin reuptake inhibitor. Pharmacotherapy 1994 14(2) 127. [PMID 8197030]... 

FIGURE 6-33. Shown here is the icon of a selective serotonin reuptake inhibitor (SSRI). In this case, four of the five pharmacological properties of the tricyclic antidepressants (TCAs) (Fig. 6-27) were removed. Only the serotonin reuptake inhibitor (SRI) portion remains thus the SRI action is selective, which is why these agents are called selective SRIs. 

Antidepressants were first introduced into the market in the 1950s with the serendipitous discovery of the antidepressant effect of two drugs initially evaluated for other medical uses Iproniazide, a monoamine oxidase inhibitor (MAOI), and Imipramine, a tricyclic antidepressant (TCA). Since then, a whole new generation of chemically and pharmacologically unrelated compounds have been introduced, which appear to be safer and better tolerated due to a more specific mechanism of action. These include selective serotonin reuptake inhibitors (SSRIs), serotonin and... 

Fluoxetine (Prozac /Lilly), paroxetine (Paxil /GlaxoSmithKilne), and sertraline (Zoloft /Pfizer) are selective serotonin reuptake inhibitors (SSRIs) and are useful in the treatment of depression. These agents potentiate the pharmacological actions of the neurotransmitter serotonin by preventing its reuptake at presynaptic neuronal membranes. In addition to its SSRI properties, venlafaxine (EfFexor /Wyeth-Ayerst) also appears to be a potent inhibitor of neuronal norepinephrine reuptake and a weak inhibitor of dopamine reuptake thereby enhancing the actions of these neurotransmitters as well. Venlafaxine is indicated for use in anxiety and depression. 

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