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Antidepressants Comparison Differences Between SSRIs and TCAs |
Selective Serotonin Reuptake Inhibitors And Tricyclic Antidepressants
Antidepressants are drugs that relieve the symptoms of depression. They were first developed in the 1950s and have been used regularly since then. There are many different families of antidepressants available today. The two most common groups are: Selective Serotonin Reuptake Inhibitors (SSRIs) and Tricyclic Antidepressants (TCAs).
Tricyclic antidepressants are a class of antidepressant drugs first used in the 1950s and are still used extensively. They are named after the drugs' molecular structure, which contains three rings of atoms. Before the introduction of SSRIs, TCAs were the standard treatment for depression.
Selective serotonin reuptake inhibitors have replaced tricyclic antidepressants as the drugs of choice in the treatment of depressive disorders, mainly because of their improved tolerability and safety if taken in overdose.
Main similarities and differences:
- SSRIs and TCAs have similar efficacy for the treatment of depression
- SSRIs have fewer anticholinergic and cardiovascular side effects
- SSRIs are better tolerated by patients
- SSRIs are safer in overdose than TCAs
History of development
Prior to the SSRIs, all psychotropic medications were the result of chance observation. The TCAs were the result of an unsuccessful attempt to improve on the antipsychotic effectiveness of phenothiazines. The other class of antidepressants, monoamine oxidase inhibitors, came from a failed attempt to develop effective antitubercular medications. The first studies of benzodiazepines were unsuccessful attempts to treat patients with schizophrenia. The SSRIs were developed in response to the need for better tolerated, safer antidepressants than the TCAs.
The nature of older chance discovery drugs is that they have many clinical effects either because they affect an site of action with broad implications for organ function or because they affect multiple site of actions. Chance discovery drugs typically will produce a number of undesired, as well as desired, effects and will have a narrower therapeutic index in comparison with a drug that was rationally developed to affect only the site of action necessary to produce the desired response.
TCAs affect multiple sites of action over a relatively narrow concentration range so that patients are likely to experience multiple effects while taking these medications. Some mechanisms of actions of TCAs can cause potentially serious effects on cardiac conduction. An overdose of TCAs of only 5 to 10 times their therapeutic dose can cause serious toxicity. Patients who have a slow clearance rate for these drugs can develop serious adverse effects on routine doses due to the accumulation of toxic concentrations.
In the case of the SSRIs, each was the product of a similar development strategy in which the goal was to produce a drug capable of inhibiting the reuptake of serotonin, but without affecting the various other neuroreceptors, affected by the TCAs. The fact that SSRIs were designed to avoid affecting these other neuroreceptors explains many of the pharmacological differences between the SSRIs and the TCAs and explains the similarities among the SSRIs.
Mechanism of action
The brain communicates with itself through the use of special chemicals called neurotransmitters such as serotonin, norepinephrine, and dopamine. There is correlation between the amount of these chemicals in the brain and a person's mood. Low levels of serotonin and norepinephrine have not been proven to cause depression but it widely believed that elevation of these chemicals is associated with improvement in mood in depressed people. Both SSRIs and TCAs work by prolonging the effects of neurotransmitters, but have different mechanism of action.
TCAs work by raising the levels of neurotransmitters serotonin and norepinephrine in the brain by slowing the rate of reabsorption by nerve cells. Unfortunately, the TCAs also block histaminic, cholinergic, and alpha1-adrenergic receptor sites, and this action leads to unwanted side effects such as weight gain, dry mouth, constipation, drowsiness, and dizziness.
TCAs act as strong inhibitors in the reuptake of both norepinephrine and serotonin. Unlike TCAs, SSRIs are highly selective: they act as weak inhibitors in the reuptake of non-serotonergic neurotransmitters such as norepinephrine, but act as strong inhibitors in the reuptake of serotonin. This selectivity is what, perhaps, accounts to the fact that there are less side effects associated with SSRIs than with TCAs.
Efficacy
SSRIs are as effective as TCAs in the treatment of major depression. They both produce overall response rates of 60% to 65%. Both the SSRIs and the TCAs produce a 25% to 30% higher response rate than placebo. Although the SSRIs have become the most commonly prescribed drugs for depression, there are clinical situations in which TCAs may be more appropriate.
Adverse effects
SSRIs affect fewer sites of action and hence cause fewer types of adverse effects than TCAs.
TCAs most commonly cause anticholinergic adverse effects, such as dry mouth, sedation, dizziness, blurred vision, constipation, and urinary retention. These effects can occasionally be quite serious or exacerbate underlying problems or tendencies in the affected organ system. Weight gain is a common complaint. The orthostatic hypotension (dizziness upon arising or otherwise rapidly changing posture) that can occur on TCAs may cause falls with resultant trauma.
The TCAs have marked effects on cardiac function and can be cardiotoxic in therapeutic dosage as well as overdose. This limits their usefulness particularly in the elderly, who are at increased risk of undetected impaired cardiac function.
With many tricyclics, the most troublesome effect with ongoing use is sedation. They are often administered at bedtime so that this effect is bearable, but it may persist into the following day.
Although the SSRIs are associated with a long list of adverse effects, in most patients they are mild and transient, rarely requiring discontinuation of therapy. Unlike the TCAs, the SSRIs do not possess significant sedative, anticholinergic, or hypotensive effects and do not have significant effects on cardiac conduction. Therefore, SSRIs are safer to use in elderly patients.
SSRIs most commonly cause:
- gastrointestinal adverse effects (nausea and diarrhoea)
- central nervous system effects (headache, dizziness, agitation, insomnia and tremor)
- sexual dysfunction.
Compared to TCAs, SSRIs have fewer anticholinergic, sedative and cardiovascular adverse effects but have more gastro-intestinal side effects. With the exception of sexual dysfunction, SSRIs side effects generally are not severe enough to make the patient noncompliant and often subside as treatment continues.
Safety in Overdose
A major benefit of the SSRIs is the much-reduced toxicity in overdose compared with the TCAs.
Overdosing on tricyclic antidepressants can lead to involvement of many organ systems but primarily affects the heart and the brain. An overdose of a TCAs requires immediate medical attention and is potentially lethal. Symptoms of an overdose usually develop within an hour of ingestion and may start with rapid heartbeat, dilated pupils, flushed face and agitation, and progress to confusion, loss of consciousness, seizures, irregular heart rate, cardiorespiratory collapse and death.
Overdosage with SSRIs is much less hazardous and less likely to be life-threatening. They do not affect intracardiac conduction. Patients have survived overdoses of each of the SSRIs that were many times their usually effective antidepressant doses without serious toxicity: no arrhythmias, no disturbance of blood pressure, no seizures, no coma, no respiratory depression. All of these adverse effects do occur with overdose of TCAs as little as 5 times their therapeutic doses.
Simplicity
Simplicity refers to how easy it is for the physician to prescribe the optimal dose and for the patient to take it. One advantage shared by both TCAs and SSRIs is that they can generally be taken once a day and be effective. However, optimal dosing with TCAs is often more problematic than with SSRIs.
Traditionally, treatment with TCAs is begun at what is usually a subtherapeutic dose and gradually titrated upward to an effective antidepressant dose. This approach is taken so that the patient can develop some tolerance to the adverse effects caused by these drugs. In contrast, SSRIs can usually be started at the effective dose from the beginning. There is generally no need to titrate the dose of the SSRIs upward in most patients.
Conclusions
SSRIs are equally as efficient as the tricyclics in the treatment of mild to moderate depression. However, the TCAs still have an important place as the first line treatment for patients with severe (melancholic/endogenous) depression.
The major clinical advantage of the SSRIs lies in their improved side effect profile and better tolerance, which is reflected in the better compliance seen even in the controlled studies. They appear safer than the TCAs on cardiotoxic measures and are associated with fewer deaths from overdosage. Increasingly clinicians are recognizing the importance of using these safer well tolerated antidepressants as first line treatment.
Yury Bayarski is the author of Price-RX.com - prescription drug price comparison website. Please follow this link if you would like to read more about tricyclic antidepressants and SSRI medications |
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