Specific serotonin reuptake

Specific Serotonin Reuptake inhibitors (SSRis). To date, the only SSRI studied in AN is fluoxetine (Prozac). During the acute refeeding phase of treatment, fluoxetine shows modest improvement in weight gain while a larger controlled study during the maintenance phase of treatment demonstrated effectiveness in the prevention of relapse. From the standpoint of side effects and toxicity, the SSRIs are clearly... 

Many antidepressant drugs have pronounced effects on sleep. Several tricyclic compounds (amitriptyline and others) have sedative actions while others (imipramine and others) are less sedative or even stimulant. Monoamine oxidase inhibitors (MAOIs) have central stimulant effects and may cause insomnia. Specific serotonin reuptake inhibitors (SSRls) and combined serotonin, noradrenaline reuptake inhibitors (SNRIs) can also cause insomnia. 

Serious toxic reactions with delirium can arise when specific serotonin reuptake inhibitors (SSRIs) are taken with other drugs that increase central and peripheral serotonergic activity. Known as the serotonin syndrome , this reaction consists of excitation, restlessness, fluctuations in consciousness, with tremor, rigidity, myoclonus, sweating, flushing, pyrexia, cardiovascular changes, and rarely coma and death (Sternbach, 1991). The syndrome has occurred when SSRIs have been combined with irreversible monoamine oxidase... 

Serotonergic drugs - antidepressants maprotUine, monoamine oxidase inhibitors, drug combinations with specific serotonin reuptake inhibitors causing the serotonin syndrome - lithium, LSD, MDMA... 

Hyttel J Citalopram pharmacological profile of a specific serotonin reuptake inhibitor with antidepressant activity. Prog Neuropsychopharmacol Biol Psychiatry 6 277-295, 1982... 

Ravindran AV, Bialik RJ, Lapierre YD Therapeutic efficacy of specific serotonin reuptake inhibitors (SSRls) in dysthymia. Can J Psychiatry 39(1) 21-26, 1994c... 

Specific serotonin reuptake inhibitors, as the class name implies, act predominantly by preventing serotonin reuptake and have more limited effects on noradrenaline reuptake. Tricyclic antidepressants in general inhibit noradrenaline reuptake, but effects on serotonin reuptake vary widely desipra-mine and protriptyline have minimal potential for raising serotonin concentrations, whereas clomipramine possesses a greater propensity for blocking serotonin reuptake than for noradrenaline. The... 

The symptoms of premenstrual syndrome (PMS), also called premenstrual dysphoric disorder, include depressed mood, anxiety, affective lability, and anger or irritability.79 Since low serotonin levels are thought to be involved in the etiology of depression, aggression, and impulsivity,80 specific serotonin reuptake inhibitors have been tested in PMS. The SSRI fluoxetine was found to be better than placebo.81 Since chronic treatment with SSRIs can influence many neuron systems other than serotonin,82 Steinberg et al.83 designed a study using tryptophan, relatively specific for its effect on serotonin, on the effects of symptoms of PMS. In a randomized controlled clinical trial, 37... 

Cooper-Kazaz R, Lerer B. Efficacy and safety of triiodothyronine supplementation in patients with major depressive disorder treated with specific serotonin reuptake inhibitors. Int J Neuropsychopharmacol 2008 11(5) 685-99. 

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. 

MAOI, monoamine oxidase inhibitor NaSSA, noradrenergic and specific serotonergic antidepressant NDRI, norepinephrine and dopamine reuptake inhibitor SARI, serotonin antagonist and reuptake inhibitor SNRI, serotonin and norepinephrine reuptake inhibitor SSRI, selective serotonin reuptake inhibitor TCA, tricyclic antidepressant. 

A breakthrough in the treatment of major depression was the discovery of fluoxetine, marketed as Prozac. Fluoxetine has a mechanism of action similar to that of imipramine with an important exception. It is a selective serotonin reuptake inhibitor, an SSRI. This strongly suggests that, in some sense, the symptoms of major depression result from a deficit in serotonin specifically. By inhibiting its reuptake from the synapse, the activity of serotonin is enhanced. Two other important drugs for major depression, sertraline (Zoloft) and paroxetine (Paxil), among several others,... 

Listing of antidepressants grouped by principal mechanism of action in the synapse. Abbreviations MAOI—irreversible = irreversible monoamine oxidase inhibitor MAOI—reversible = reversible monoamine oxidase inhibitor NDRl = norepinephrine/ dopamine reuptake inhibitor NRI = norepinephrine reuptake inhibitor NSRl = norepinephrine/serotonin reuptake inhibitor NSSA = norepinephrine/specific serotonin agonist SRI = serotonin reuptake inhibitor SRl/serotonin-2 blocker = serotonin reuptake inhibitor and serotonin-2 receptor antagonist. 

Nefazodone (Serzone). Nefazodone works by weakly blocking serotonin reuptake and by blocking serotonin-2 receptors. The receptor blockade produces more specific serotouiu activity aud so reduces mauy serotonin-associated side effects. In particular, uefazodoue does not commonly induce anxiety or sexual dysfunction like the SSRIs. 

It should be possible to treat the disease by increasing the concentration of the neurotransmitter in the synaptic cleft. There are, in principle, three ways in which this could be achieved, (i) Neurotransmitter synthesis could be increased, (ii) The rate of exocytosis could be increased, (iii) Removal of neurotransmitter from the synapse could be inhibited. Drugs that affect process (iii) have been developed. The tricyclic antidepressants and the specific serotonin (5-hydroxytryptamine) reuptake inhibitors (abbreviated to SSRIs) inhibit uptake of the neurotransmitter into the presynaptic on postsynaptic neurone. The most prescribed SSRI is fluoxetine (Prozac). 

Specific inhibitors of noradrenaline and serotonin reuptake (SNRIs)... 

Young TJ, et al. (2003) Antifungal activity of selective serotonin reuptake inhibitors attributed to non-specific cytotoxicity. J. Antimicrob. Chemofher. 51 1045-1047. 

Briley, M. (1998). Milnacipran, A Well-Tolerated Specific Serotonin and Norepinephrine Reuptake Inhibiting Antidepressant, CNS Drug Reviews, 4 137-148. 

The selective serotonin reuptake inhibitors (SSRI) have been used in adults for a wide variety of disorders, including major depression, social anxiety (social phobia), generalized anxiety disorder (GAD), eating disorders, premenstrual dysphoric disorder (PMDD), post-traumatic stress disorder (PTSD), panic, obsessive-compulsive disorder (OCD), trichotillomania, and migraine headaches. Some of the specific SSRI agents have an approved indication in adults for some of these disorders, as reviewed later in this chapter. The SSRIs have also been tried in children and in adults for symptomatic treatment of pain syndromes, aggressive or irritable ( short fuse ) behavior, and for self-injurious and repetitive behaviors. This chapter will review general aspects of the SSRIs and discuss their approved indications in children and adolescents. 

Tricyclic antidepressants are still prescribed today, but some patients experience side effects such as dry mouth, blurry vision, constipation, and other uncomfortable conditions. Other antidepressants have since been found that induce fewer side effects. One of the most popular is fluoxetine, which is marketed under the trade name Prozac. This drug, along with Zoloft and other antidepressants, are known to inhibit reuptake proteins specifically for serotonin. As a result, these drugs are called selective serotonin reuptake inhibitors, or SSRIs. Although some concerns have appeared because of a possible risk of suicide in young patients who take Prozac, these drugs are commonly prescribed and have proved highly effective in millions of patients. 

Although postsynaptic DA agonists and presynaptic Dj autoreceptor antagonists share a common property of enhancing DA transmission, Dj autoreceptor agonists have been developed specifically to block DA transmission as an alternative approach to antipsychotic therapy (Benkert et al. 1992). A variety of such compounds are available (Seyfried and Boettcher 1990), four of which—talipexole, pramipexole, roxindole, and OPC-4392 —have been evaluated as antipsychotics in schizophrenic patients (Benkert et al. 1992). Only roxindole has been tested in depression, and then only in two uncontrolled pilot studies over 4 weeks of treatment (Benkert et al. 1992 M. Kellner et al. 1994). Response rates similar to those of imipramine were observed, with a fast onset of action in some patients. Roxindole s antidepressant action may lie in its ability to selectively stimulate supersensitive postsynaptic Dj receptors, and thereby enhance DA function, or in its additional properties as an inhibitor of serotonin reuptake and as a 5-HT, receptor agonist (Benkert et al. 1992 Seyfried et al. 1989). 

The agents in this class demonstrate the common feature of specific inhibition of serotonin reuptake without significant effects on norepinephrine and dopamine reuptake. These agents also lack direct agonist or antagonist activity on any neurotransmitter receptor. 

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