Selective serotonin reuptake adverse effects

MDMA overdose as well as the concomitant consumption of selective serotonin reuptake inhibitors (SSRI) with other dmgs that exert serotoninergic effects (such as inhibitors of monoamine oxidase) can rapidly lead to the serotonin syndrome. Its symptoms, which are reversible upon cessation, of the drug include confusion, muscle rigidity in the lower limbs, and hyperthermia suggesting an acute reaction to serotonin overflow in the CNS. Blocking the function of SERT outside the brain causes side effects (e.g., nausea), which may be due to elevated 5HT however , impairment of transporter function is not equivalent to direct activation of 5HT recqrtors in causing adverse effects such as fibrosis and pulmonary hypertension. 

A number of non-hormonal therapies have been studied for symptomatic management of vasomotor symptoms, including antidepressants [e.g., selective serotonin reuptake inhibitors (SSRIs) and venlafaxine], herbal products (e.g., soy, black cohosh, and dong quai), and a group of miscellaneous agents (e.g., gabapentin, clonidine, and megestrol). The choice of therapy depends on the patient s concomitant disease states, such as depression and hypertension, and the risk for potential adverse effects. 

Dizziness, vertigo, nausea, vomiting, constipation, and lethargy are all relatively common adverse events. These effects are more pronounced for several days after initiation and following upward dose titration. Seizures have been reported rarely the risk is dose-related and appears to increase with concomitant use of antidepressants, such as tricyclic antidepressants or selective serotonin reuptake inhibitors. Tramadol should be avoided in patients receiving monoamine oxidase (MAO) inhibitors because tramadol inhibits the uptake of norepinephrine and serotonin. 

In many clinical trials a positive control of a clinically established drug is often used for comparison purposes for example, a novel selective serotonin reuptake inhibitor (SSRI), may be compared with a more established tricyclic antidepressant, such as imipramine. The aim is to see whether the new SSRI is more efficacious or has fewer adverse side effects than the more established tricyclic (Chapter 12). In many such comparisons the new and older treatments are equally efficacious at relieving depression, but the newer drugs display fewer side effects this means that they are better tolerated by patients, so that they are more willing to continue taking the tablets. The high rates of compliance also mean that, in overall terms, newer drugs with fewer side effects tend to be more efficacious. 

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. 

The most commonly used therapies for anxiety and depression are selective serotonin reuptake inhibitors (SSRIs) and the more recently developed serotonin noradrenaline reuptake inhibitors (SNRIs). SSRIs, which constitute 60% of the worldwide antidepressant and antianxiety market, are frequently associated with sexual dysfunction, appetite disturbances and sleep disorders. Because SSRIs and SNRIs increase 5-HT levels in the brain, they can indirectly stimulate all 14 serotonergic receptor subtypes [2,3], some of which are believed to lead to adverse side effects associated with these drugs. Common drugs for short-term relief of GAD are benzodiazepines. These sedating agents are controlled substances with addictive properties and can be lethal when used in combination with alcohol. The use of benzodiazepines is associated with addiction, dependency and cognitive impairment. 

In trials of hospitalized patients tricyclic antidepressants have generally been more efficacious than selective serotonin reuptake inhibitors (SSRIs). Otherwise there are no overall differences between the drugs in terms of tolerability or efficacy in primary care settings. After reviewing 15 trials it was concluded that drags are effective in the treatment of dysthymia with no differences between and within class of drugs. Tricyclic antidepressants are more likely to cause adverse events and dropouts. As dysthymia is a chronic condition, there remains little information on quality of life and medium or longterm outcome. 

Preskorn, S.H. (2000) The adverse effect profiles of the selective serotonin reuptake inhbitors relationship to in vitro pharmacology. J Psychiatri Practi 6 153-157. 

Psychodynamic supportive psychotherapy (n = 107) has been compared with psychotherapy plus medication (n = 101) in patients with major depressive disorder (93). The medications included venlafaxine, selective serotonin reuptake inhibitors, nortriptyline, and nortriptyline plus lithium. Lithium was used as an augmentation strategy in the patients who took lithium and nortriptyline (number not given). There were no differences in outcomes between the two treatment groups. No adverse effects specific to lithium were reported. 

Olanzapine, mean dose 5.4 mg/day, has been given to 21 patients with apathy in the absence of depression after long-term treatment with selective serotonin reuptake inhibitors for non-psychotic depression in an open, flexible-dose study (16). The more frequent adverse effects were sedation (n = 12), increased appetite (n = 8), stiffness (n = 7), edema (n = 6), and dry mouth (n = 5). 

Olanzapine was effective in an open trial in 10 patients with obsessive-compulsive disorder refractory to selective serotonin reuptake inhibitors, who were given additional olanzapine they had minimal adverse effects, primarily sedation (27). 

There have been reports that selective serotonin reuptake inhibitors, which inhibit CYP1A2, increase plasma olanzapine concentrations (SEDA-24, 71 SEDA-26, 63). In a recent open add-on trial, 21 patients with obsessive-compulsive disorder unresponsive to treatment with paroxetine 60 mg/day for at least 12 weeks, took additional olanzapine 10 mg/day (280). Steady-state plasma concentrations of paroxetine were not changed, and 7 patients were rated as responders at final evaluation. Sedation (n = 12), weight gain up to 3 kg (n = 8), dry mouth (n = 6), and constipation (n = 3) were the most frequent adverse effects. 

Aspirin produces an antipyretic and anti-inflammatory effect primarily by irreversibly inhibiting cyclooxygenase (thus having similar effects to NSAIDs). It possesses an antiplatelet effect that may have additive effect with other drugs with a similar effect (e.g, selective serotonin reuptake inhibitors) and those which affect other aspects of blood clotting. The risk of interactions and adverse effects are reduced by using a lower dose (e.g. 75 mg) fortunately, a full antiplatelet effect is seen at this dose. This is considered in Part 1, Cardiovascular Drugs. 

St. John s wort also exhibits anti-inflammatory and antibacterial activity. Reports of antiviral activity arc unsubstantiated. The main adverse effect with St. John s wort is severe phototoxicity. A sunbum-like condition may occur at normal dosages. St. John s wort. should never be taken with MAOIs because of the risk of potentiation of the effects. Selective serotonin reuptake inhibitors (SSRIs) likewise should not be taken with St. John s wort because of the ri.sk of serotonergic syndrome. 

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%). 

The uses, drug interactions, and adverse effects of the monoamine oxidase inhibitor tricyclic, selective serotonin reuptake inhibitor, and heterocyclic antidepressants are discussed. 

Herbalists also believe that combining herbs improves efficacy and reduces adverse effects. When compounded by knowledgeable practitioners, some of the remedies do make sense. The combination of Devil s claw, white willow, and tumeric, all agents with antiinflammatory effects, is rational, and quite probably effective. But combining St. John s Wort, which contains a selective serotonin reuptake inhibitor, with Ephedra, which causes increased catecholamine release, is both dangerous and ill advised. 

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