- Antidepressants are drugs which are used to treat depression i.e. can elevate mood in depressive illness.
- Antidepressant drugs potentiate, either directly or indirectly, the actions of norepinephrine and/or serotonin (5-HT) in the brain.
- Biogenic amine theory (most accepted theory) proposes that depression is due to a deficiency of monoamines, such as norepinephrine and serotonin, at certain key sites in the brain. It states that inhibition of reuptake can enhance neuro-transmission, presumably by slowing clearance of the transmitter from the synapse and prolonging the dwell-time of the transmitter in the synapse.
- Enhancing neurotransmission may subsequently lead to adaptive changes. Reuptake inhibitors inhibit either SERT, the neuronal serotonin transporter; NET, the neuronal norepinephrine (NE) transporter; or both.
- Practically all antidepressants affect monoaminergic transmission in the brain in one way or the other and many of them have other associated properties.
On the basis of mechanism of action, antidepressant drugs can be classified as follows:
1. Selective serotonin reuptake inhibitors (SSRIs)
- Selective serotonin reuptake inhibitors (SSRIs) are a group of antidepressant drugs that specifically inhibit serotonin reuptake, having 300- to 3000-fold greater selectivity for the serotonin transporter, as compared to the norepinephrine transporter.
- Moreover, the SSRIs have little blocking activity at muscarinic, α-adrenergic, and histaminic H1 receptors. Therefore, common side effects associated with TCAs, such as orthostatic hypotension, sedation, dry mouth, and blurred vision, are not commonly seen with the SSRIs.
- Because they have different adverse effects and are relatively safe even in overdose, the SSRIs have largely replaced TCAs and monoamine oxidase inhibitors (MAOIs) as the drugs of choice in treating depression.
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2. Serotonin norepinephrine reuptake inhibitors (SNRIs)
- Serotonin norepinephrine reuptake inhibitors (SNRIs) are a group of antidepressant drugs that inhibit the reuptake of both serotonin and norepinephrine.
- SNRIs may be effective in treating depression in patients in whom SSRIs are ineffective. Furthermore, depression is often accompanied by chronic painful symptoms, such as backache and muscle aches, against which SSRIs are also relatively ineffective.
- Both SNRIs and the TCAs, with their dual inhibition of both serotonin and norepinephrine reuptake, are sometimes effective in relieving pain associated with diabetic peripheral neuropathy, postherpetic neuralgia, fibromyalgia, and low back pain.
- The SNRIs, unlike the TCAs, have little activity at α-adrenergic, muscarinic, or histamine receptors and, thus, have fewer of these receptor-mediated adverse effects than the TCAs.
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3. Tricyclic antidepressants (TCAs)
- Tricyclic antidepressants (TCAs) are a group of antidepressant drugs that block norepinephrine and serotonin reuptake into the presynaptic neuron.
- The TCAs block norepinephrine and serotonin reuptake into the presynaptic neuron and, thus, if discovered today, might have been referred to as SNRIs, except for their differences in adverse effects relative to this newer class of antidepressants.
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- Maprotiline and amoxapine are related tetracyclic antidepressant agents and are commonly included in the general class of TCAs.
4. Atypical antidepressants
- Atypical antidepressants are a mixed group of antidepressant agents that have actions at several different sites.
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5. Mono-amine Oxidase inhibitors (MAOIs)
- Monoamine oxidase inhibitors (MAOIs) may irreversibly or reversibly inactivate the enzyme Monoamine oxidase (MAO), permitting neurotransmitters to escape degradation and, therefore, to accumulate within the presynaptic neuron and leak into the synaptic space.
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Antidepressant drugs can be used clinically in following way:
- Primarily indicated as anti-depressant drug for treating depression (major/endogenous depression).
- Effective in a number of psychiatric disorders including obsessive compulsive disorder OCD, panic disorder, social phobia, generalized anxiety disorder (anxiolytic), social anxiety disorder, premenstrual dysphoric disorder, body dysmorphic disorder, compulsive buying and kleptomania.
- Approved for the treatment of posttraumatic stress disorder (PTSD) &
- Approved for Attention deficit-hyperactivity disorder ADHD in children.
- Effective in relieving pain associated with diabetic peripheral neuropathy, postherpetic neuralgia, fibromyalgia, panic attacks, low back pain & stress urinary incontinence in women.
- May be used to control bed-wetting (enuresis) in children older than 6 years of age.
- May be used to help prevent migraine headache.
- Used to improve outlook on life and to feel good.