Types of Antidepressants and How to Withdraw Them Safely

Introduction

Antidepressants are a class of medications that are prescribed to ease the symptoms of depression, anxiety disorder, and other medical conditions. Antidepressant drugs work by correcting the imbalance in the chemical messengers in the brain to modulate the mood and behavior of the individual. Various types of antidepressants are available and are prescribed accordingly.

What Are Antidepressants?

Antidepressants are a group of medications that treat depression, anxiety disorders, and chronic pain. It is also given to manage addictions. They are given to manage social phobia, obsessive-compulsive disorder, panic disorder, generalized anxiety disorder, and post-traumatic disorder.

Neurotransmitters are chemical messengers that carry signals from one neuron (nerve cell) to another. Various neurotransmitters are present in the body. Serotonin, dopamine, and norepinephrine are a few types of neurotransmitters. Antidepressants work to increase these neurotransmitters to modulate mood and behavior, thereby treating depression and other disorders.

What Are the Types of Antidepressants?

Various types of antidepressants are available with slightly different mechanisms of action. The types of antidepressants include

• Selective Serotonin Reuptake Inhibitors (SSRIs).

• Serotonin or Norepinephrine Reuptake Inhibitors (SNRIs).

• Tricyclic Antidepressants (TCAs).

• Atypical antidepressants.

• Serotonin Modulators.

• Monoamine Oxidase Inhibitors (MAOIs).

• NMDA (N-Methyl-D-Aspartate) antagonists.

1) Selective Serotonin Reuptake inhibitors (SSRIs).

Mechanism of Action - Selective serotonin reuptake inhibitors block the reabsorption of serotonin into the nerve cells and prolong the serotonergic neurotransmission to improve the transmission of information between the nerve cells. They increase the level of serotonin in the brain. They are the first line of drugs for the treatment of depression.

Types - SSRIs include the following drugs:

• Sertraline.

• Fluvoxamine.

• Fluoxetine.

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• Paroxetine.

• Citalopram.

• Escitalopram.

Uses - SSRIs are given to treat depression and anxiety disorders. They are also used for treating panic disorder, generalized anxiety disorder, obsessive-compulsive disorder, agoraphobia, social phobia, bulimia nervosa, and post-traumatic stress disorder.

Side Effects - They cause side effects like sexual dysfunction, headache, and QTc prolongation (QTc prolongation indicates an extended interval between the contraction and relaxation of the heart on electrocardiography). They are not recommended for pregnant, breastfeeding women and individuals under 18.

2) Serotonin or Norepinephrine Reuptake Inhibitors (SNRIs)

Mechanism of Action - Serotonin or norepinephrine reuptake inhibitors block the reabsorption of serotonin and norepinephrine in the synapse (junction between two nerve cells where information is passed from one cell to another cell) and increase the stimulation of postsynaptic receptors.

Types - SNRIs include the following drugs:

• Venlafaxine.

• Desvenlafaxine.

• Duloxetine.

• Milnacipran.

• Levomilnacipran.

Uses - SNRIs are second-line drugs used in the treatment of depression. They are similar to SSRIs and are used to treat anxiety disorders, major depressive disorder, obsessive-compulsive disorder, attention-deficit hyperactivity disorder, chronic neuropathic pain, fibromyalgia syndrome, and menopausal symptoms.

Side Effects - SNRIs cause side effects like hypertension, diaphoresis, headache, and bone resorption. They should not be combined with another antidepressant drug because it leads to serotonin syndrome, which causes severe neuromuscular and autonomic symptoms.

3) Tricyclic Antidepressants (TCAs)

Mechanism of Action - Tricyclic antidepressants work by inhibiting the reabsorption of norepinephrine and serotonin at the presynaptic membrane.

Types - Tricyclic antidepressants include the following drugs:

• Amitriptyline.

• Clomipramine.

• Doxepin.

• Imipramine.

• Trimipramine.

• Desipramine.

• Nortriptyline.

• Protriptyline.

• Maprotiline.

• Amoxapine.

Uses - Tricyclic antidepressants are used to treat major depressive disorder. It also treats obsessive-compulsive disorder, insomnia, anxiety, and chronic pain like neuropathic pain. It is commonly used in migraine prophylaxis. It treats conditions like myofascial pain, diabetic neuropathy, and postherpetic neuralgia. Tricyclic antidepressants are the second-line treatment for fibromyalgia and nocturnal enuresis in children.

Side Effects - Tricyclic antidepressants also have an affinity for muscarinic M1 receptors and histamine H1 receptors, so they cause sedation and anticholinergic side effects. They also cause side effects like dry mouth, orthostatic hypotension, seizures, constipation, urinary retention, and QRS prolongation (which indicates delayed ventricular electrical activation on electrocardiography).

4) Atypical Antidepressants

Mechanism of Action - Atypical antidepressants have multiple mechanisms of action. Bupropion inhibits the reabsorption of dopamine and norepinephrine at the presynaptic cleft. Agomelatine promotes dopamine and serotonin release. Mirtazapine promotes the release of norepinephrine into the synapse and increases norepinephrine and dopamine in the brain's cortical regions.

Types - Atypical antidepressants include the following drugs:

• Bupropion.

• Mirtazapine.

• Agomelatine.

Uses - Atypical antidepressants treat depression in patients with inadequate responses or side effects to first-line treatment with selective serotonin reuptake inhibitors.

Side Effects - Sedation, weight gain, hepatotoxicity, and seizures are the side effects of atypical antidepressants.

5) Serotonin Modulators

Mechanism of Action - Serotonin modulators inhibit the presynaptic reabsorption of serotonin and norepinephrine and increase serotonergic transmission.

Types - Serotonin modulators include the following drugs:

• Nefazodone.

• Trazodone.

• Vilazodone.

• Vortioxetine.

Uses - Serotonin modulators are prescribed for major depressive disorder.

Side Effects - The side effects of serotonin modulators are acute hepatitis with cholestasis, centrilobular necrosis, diarrhea, nausea, sedation, and priapism.

6) Monoamine Oxidase Inhibitors (MAOIs)

Mechanism of Action - Monoamine oxidase inhibitors work by inhibiting the monoamine oxidase enzyme, which is responsible for catabolizing dopamine, norepinephrine, and serotonin.

Types - Monoamine oxidase inhibitors include the following drugs:

• Selegiline.

• Moclobemide.

• Tranylcypromine.

• Isocarboxazid.

• Phenelzine.

Uses - Monoamine oxidase inhibitors are given to treat depression and other nervous system disorders like social phobia, panic disorder, and depression with atypical features.

Side Effects - Monoamine oxidase inhibitors cause side effects like serotonin syndrome and sexual dysfunction.

7) NMDA (N-Methyl-D-Aspartate) antagonists

Mechanism of Action - Glutamate is an excitatory neurotransmitter. An alteration of glutamate and gamma-aminobutyric acid activity has been observed in depression. NMDA antagonists bind to the glutamate site to inhibit its action.

Types - NMDA antagonists include the following drugs:

• Esketamine.

• Dextromethorphan.

Uses - NMDA receptor antagonists treat resistant depression and major depressive disorder.

Side Effects - Paranoid delusions, confusion, hallucinations, agitation, ataxia, and learning and memory deficits.

How to Safely Overcome Antidepressants?

Antidepressants are prescription drugs that should be consumed and stopped under the guidance of a physician. It is important to talk to the doctor before discontinuing the antidepressants. The doctor slowly tapers the dose of antidepressants and completely cuts back the drugs over a period. The doctor also changes short-acting antidepressants to long-acting depressants to ease the transition. This is the safest method to overcome antidepressants to prevent withdrawal symptoms. Drugs are prescribed for withdrawal symptoms like nausea or insomnia.

Conclusion

Antidepressants are a group of prescription drugs that treat depression. Multiple antidepressants with slightly different action mechanisms are available and used accordingly. It is important to consult a physician before consuming and discontinuing the antidepressants.