Specific serotonin reuptake inhibitors SSRIs

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... 

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... 

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. 

More recent developments in psychopharmacology that are of interest include atypical antipsychotic drugs, new antidepressants, specifically selective serotonin reuptake inhibitors (SSRIs), and drugs for the treatment of Alzheimer s disease. 

Another approach to correct neurotransmission is to inhibit the reuptake of the neurotransmitters into their presvnaptic endings. If the presynaptic reuptake mechanism of a neurotransmitter is blocked then more of the neurotransmitter will stay in the synaptic cleft and be functionally available. Many antidepressant drugs, called reuptake inhibitors , are thought to act via this mechanism. If selective for serotonin they are called selective serotonin reuptake inhibitors (SSRIs, Chapter 1), but if selective for both serotonin and noradrenaline they are called serotonin noradrenaline reuptake inhibitors (SNRIs). Most older antidepressants, such as the tricyclic compounds amitriptyline, imipramine and clomipramine, have little specificity for any of the neurotransmitters fluoxetine, paroxetine, citalopram and a few others are specific for serotonin venlafaxine is a representative of the SNRIs. A more recent mixed-uptake inhibitor is mirtazepine, and some similar compounds are about to be launched. 

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. 

Despite the diagnostic challenges that remain in trying to understand the nature of MDD in children and adolescents, advances in its treatment has progressed considerably since the last edition of this textbook. Over this interval, selective serotonin reuptake inhibitors (SSRIs) have superseded TCAs as the treatment of first choice based both on efficacy and safety considerations. As in adults, specific psychotherapies (cognitive therapy, cognitive-behavioral therapy, and interpersonal therapy) may be as effective as antidepressant medication, at least in mild to moderate depression in children and adolescents ( 111, 112). Also, evidence indicates that depression in children and adolescents may be more influenced than is depression in adults by psychosocial variables such as peers and family, as well as other environmental factors (113). 

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... 

The selective serotonin-reuptake inhibitors (SSRI) are a new group of chemically unique antidepressant drugs that specifically inhibit serotonin reuptake (see Figure 12.3). This contrasts with the tricyclic antidepressants that nonselectively inhibit the uptake of norepinephrine, and serotonin, and block muscarinic, H histaminic and a -adrenergic receptors. Compared with tricyclic antidepressants, the SSRIs cause fewer anticholinergic effects and lower cardiotoxicity. However, the newer serotonin reuptake inhibitors should be used cautiously until their long-term effects have been evaluated. 

Adults with bulimia nervosa may be offered a trial with an antidepressant drug. Patients should be informed that antidepressant drugs can reduce the frequency of binge eating and purging. Selective serotonin reuptake inhibitors (SSRIs), and specifically fluoxetine, are the drugs of first choice for the treatment of bulimia... 

Serotonin Usually inhibitory helps control mood, influences sleep, and inhibits pain pathways in the spinal cord. Secreted by subcortical structures into hypothalamus, brain, and spinal cord. There are many subtypes of serotonin receptors. Diffuse and widespread symptoms depression, headache, diarrhea, constipation, sexual dysfunction, and other medical symptoms. The selective serotonin reuptake inhibitors (SSRIs), the most commonly used antidepressants, work specifically on this neurotransmitter system. 

Fluoxetine and other selective serotonin reuptake inhibitors (SSRIs) have been associated with increasing suicidal ideation in some populations of patients. Recent studies have led the British Department of Health to warn physicians against using paroxetine off label. Fluoxetine was specifically exempted from this recommendation. Long-term studies of patients with depression who were treated with fluoxetine have shown it to be fairly well tolerated. Primary adverse effects include nausea (23%), headache (21%), and insomnia (20%). 

SSRI Antidepressants. Selective serotonin reuptake inhibitor (SSRI) antidepressants decrease REM sleep. This is ascribed to the increase in postsynaptic serotonin levels. Several drugs, including fluoxetine, that specifically inhibit the reuptake of serotonin induce wakefulness during sleep and increase alertness during the day. 

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... 

The treatment of MDD corresponds to three stages acute phase, continuation phase, and maintenance phase. The gross treatment options should follow the strategies listed in Scheme 9.3. The following are only suggestions, which are based mainly on specific data from accumulated research. The selective serotonin reuptake inhibitors (SSRIs) and venlafaxine are usually considered as first-line treatments. Amitriptyline and clomipramine are second-line treatments. Other tricyclic antidepressants (TCAs) and the monoamine oxidase inhibitors (MAOIs) are third-line treatments. 

Selective serotonin reuptake inhibitors (SSRIs) are the first-line therapy for PTSD. Efficacy for fluoxetine, paroxetine, and sertraline has been demonstrated in well-designed double-blind placebo-controlled studies to reduce all symptom domains (intrusive recollection, avoidance/numbness, and hyperarousal). - Other treatment options include the tricyclic antidepressants (TCAs) amitriptyline and imipramine and the irreversible monoamine oxidase inhibitor (MAOl) phenelzine, which have been shown to reduce re-experiencing. However, in comparison with SSRIs, TCAs and phenelzine are associated with a higher incidence of side-effects, risk of overdose, and poor compliance. Alprazolam has demonstrated anecdotal efficacy however, regular use of benzodiazepines is not recommended. Benzodiazepines can be used on an as-needed basis for specific symptoms (e.g. sleep disturbances). CBT has shown beneficial effects in relatively well-controlled studies, while the results with exposure therapy are... 

Several selective serotonin reuptake inhibitors (SSRIs), including escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline (Fig. 22.21), are effective as first-line treatment cf seme anxiety disorders, with the purported advantage that they lack the addictive preperties cf benzediazepines (135). Specifically, the SSRIs have been shown to be effective in obsessive-ccmpulsive diserder (139), panic disorder (140), and social phobia (141). The mechanism of action of these agents in anxiety may differ with their role in the treatment of depression however,... 

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,... 

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. 

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