Tricyclic antidepressants risks

Cocaine and desipramine inhibit the reuptake of monoamine neurotransmitters whereas amphetamine, which is a phenylalkylamine - similar in structure to the catecholamines, see Fig. 4 - competes for uptake and more importantly, evokes efflux of the monoamine neurotransmitters. All of them exert antidepressant effects. Cocaine and amphetamine are addictive whereas tricyclic antidepressants and their modern successors are not. The corollaty of the addictive properties is interference with DAT activity. Blockade of DAT by cocaine or efflux elicited by amphetamine produces a psychostimulant effect despite the different mechanisms even the experienced individual can hardly discern their actions. Because of the risk associated with inhibiting DAT mediated dopamine clearance the antidepressant effects of psychostimulants has not been exploited. 

Use of die MAOIs must be discontinued 2 weeks before the administration of die SSRIs. When the SSRIs are administered witii die tricyclic antidepressants, tiiere is an increased risk of toxic effects and an increased tiierapeutic effect. When sertraline is administered witii a MAOI, a potentially fatal reaction can occur. Sjymptoms of a serious reaction include hyper-tiiermia, rigidity, autonomic instability witii fluctuating vital signs and agitation, delirium, and coma Sertraline blood levels are increased when administered witii cimetidine. 

Older men with prostatic enlargement are at increased risk for urinary retention when they take the tricyclic antidepressants. 

Serious adverse effects of epinephrine potentially occur when it is given in an excessive dose, or too rapidly, for example, as an intravenous bolus or a rapid intravenous infusion. These include ventricular dysrhythmias, angina, myocardial infarction, pulmonary edema, sudden sharp increase in blood pressure, and cerebral hemorrhage. The risk of epinephrine adverse effects is also potentially increased in patients with hypertension or ischemic heart disease, and in those using (3-blockers (due to unopposed epinephrine action on vascular Ui-adrenergic receptors), monoamine oxidase inhibitors, tricyclic antidepressants, or cocaine. Even in these patients, there is no absolute contraindication for the use of epinephrine in the treatment of anaphylaxis [1,5,6]. 

Guidelines agree that when antidepressants must be used, they should be combined with a mood-stabilizing drug to reduce the risk of mood switch to hypomania or mania.17,41 The question of which antidepressant drugs are less likely to cause a mood switch is not resolved. Anecdotal reports suggested bupropion may be less likely to cause this effect, but systematic reviews have not supported this conclusion. Prevailing evidence recommends that tricyclic antidepressants be avoided.41,43... 

The tricyclic antidepressants (TCAs), such as imipramine, can alleviate symptoms of ADHD. Like bupropion, TCAs likely will improve symptoms associated with comorbid anxiety and depression. The mechanism of action of TCAs is in blocking norepinephrine transporters, thus increasing norepinephrine concentrations in the synapse the increase in norepinephrine is believed to alleviate the symptoms of ADHD. TCAs have been demonstrated to be an effective non-stimulant option for ADHD but less effective than stimulants. However, their use in ADHD has declined owing to case reports of sudden death and anticholinergic side effects6,13 (Table 39-3). Further, TCAs may lower seizure threshold and increase the risk of car-diotoxicity, (e.g., arrythmias). Patients starting on TCAs should have a baseline and routine electrocardiograms. 

A number of medications have been associated with an increased risk of falling, including drugs affecting mental status such as antipsychotics, benzodiazepines, tricyclic antidepressants, sedative-hypnotics, anticholinergics, and corticosteroids. Some cardiovascular and antihypertensive drugs also can contribute to falls, especially those causing orthostatic hypotension.9... 

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. 

Before the arrival of the new antidepressants, the older tricyclic antidepressants were widely used to treat depression and agitation in demented patients. They have now largely been abandoned in these patients as their prominent anticholinergic effects tend to worsen dementia and the increased risk for cardiac toxicity can be especially dangerous in geriatric patients. 

Antidepressants. Depression after TBl is routinely treated with antidepressant medicines. Although all antidepressants are potentially helpful, antidepressants prone to burdensome side effects, particularly sedative and anticholinergic side effects, should generally be avoided, as they are likely to be tolerated poorly by these patients. In addition, antidepressants that may increase the risk for seizure, such as many of the older tricyclic antidepressants (TCAs) and bupropion (Well-butrin), should be avoided because post-TBl patients as a rule are already more vulnerable to seizures. 

Tramadol is an opioid analgesic and when given to patients who are also receiving imipramine (a tricyclic antidepressant), there is an increased risk of central nervous system toxicity. The risk of occurrence of sedation is increased. 

Tricyclic antidepressants are notorious for their risk to be involved in drug-drug interactions. Additive anticholinergic effects can be expected in combination with antihistamines, antipsychotics and anticholinergic-type anti-Parkinson agents. Hepatic enzyme-inducing agents increase their hepatic metabolism while enzyme inhibitors may potentiate the effects of tricyclics. Concomitant use with monoamine oxidase inhibitors will produce hypertension, hyperpyrexia and convulsions. 

Agents from this class of antidepressants are selective blockers of the re-uptake of serotonin at presynaptic neurones and have little if any effects on muscarinic, histaminergic, adrenergic or serotonergic receptors. They are as effective as the tricyclic antidepressants in the management of depressive disorders, but have less cardiovascular effects. They have less anticholinergic activity and because of their lower risk of cardiotoxicity in overdose they... 

Serotonin-specific inhibitors (SSRI) include fluoxetine, paroxetine, sertraline, citalopram and others. They are not more effective than the tricyclic antidepressants but may suit some patients better and are generally safer in overdose (see Geddes et al., 1999). While the SSRIs are devoid of the cardiac effects (membrane stabilisation, inhibition of conduction) of the tricyclics in overdose, they increase the risk of hemorrhage into the gut or brain. 

Geriatric Considerations - Summary Bupropion has several advantages as an antidepressant agent for use in older adults. It has neither the anticholinergic or cardiac toxicities of the tricyclic antidepressants, and has fewer sexual side effects than selective serotonin reuptake inhibitors. Because this drug may lower seizure threshold, it should be used with caution in older adults with increased risk of seizures (e.g., previous stroke, early-onset Alzheimer s disease). 

Mirtazapine poses a higher risk of seizures than tricyclic antidepressants, especially in those with no previous history of seizures. 

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. 

Antidepressants are as effective as benzodiazepines in the treatment of panic disorder. Moreover, antidepressants do not have the same risks of tolerance and dependency that are associated with benzodiazepine treatment. However, antidepressants take longer to work, so that significant improvement might not be observed until after a month of treatment. Although tricyclic antidepressants have been approved for the treatment of panic disorder, the effectiveness of selective serotonin reuptake inhibitors (SSRIs) in its treatment has led them to become the favored treatment among antidepressant drugs. 

In clinical practice, a number of patients with SRI-resistant OCD receive simultaneous treatment with two potent SRls. Apart from encouraging case reports of coadministering fluoxetine and clomipramine in adolescents [Simeon et al. 1990] and adults [Browne et al. 1993] with OCD, the efficacy and safety of this approach have not been subjected to rigorous examination. Because of the risks associated with fluoxetine-induced elevations in plasma levels of tricyclic antidepressants, caution should be exercised when these drugs are used concurrently [Rosenstein et al. 1991]. Clomipramine s potential for lowering seizure threshold is of particular concern, making it advisable to measure clomipramine plasma levels before and after addition of another SRI. 

Some patients with bipolar disorder will need antidepressants. Although the switch rate into mania or induction of rapid cychng by antidepressants is controversial, these agents do appear to present a risk for some patients, often with devastating consequences. Therefore, when a patient with bipolar disorder is prescribed an antidepressant, it should only be in combination with a medication that has established antimanic properties. Controlled comparative data on the use of specific antidepressant drugs in the treatment of bipolar depression are sparse. Current treatment guidelines extrapolate from these few studies and rely heavily on anecdotal chnical experience. Overah, tricyclic antidepressants should be avoided when other viable treatment options exist. Electroconvulsive therapy should be considered in severe cases. 

Preskorn SH, Jerkovich GS. Central nervous system toxicity of tricyclic antidepressants phenomenology, course, risk factors and role of therapeutic drug monitoring. J Clin Psychopharmacol 1990 10 88-95. 

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