Antidepressant Drugs Overview

Anti-Depressants Drugs

• Antidepressants are substances used to treat depression, elevate mood, and improve the sense of well-being.
• Actions of antidepressants include elevating mood, improving sleep, increasing appetite, increasing activity, helping patients become more sociable, and decreasing anxiety.

Classifications

• Tricyclic & tetracyclic antidepressants (TCAs)
• Monoamine oxidase inhibitors (MAOIs)
• Selective serotonin reuptake inhibitors (SSRIs)
• Novel or atypical antidepressants (post SSRIs)

Tricyclic & Tetracyclic Antidepressants (TCAs)

• Action of TCAs: Depressed patients have a decrease in serotonin, dopamine, and norepinephrine.
• TCAs block the reuptake of neurotransmitters, 5HT & NE, in the pre-synapse. This allows 5HT & NE to remain and be active longer in the synapse.
• Non-therapeutic actions:
  • Block alpha receptors leading to vasodilation and orthostatic hypotension.
  • Block histamine receptors leading to sedation and weight gain.
  • Block acetylcholine receptors leading to anticholinergic side effects

Indications of TCAs

• Treatment of major depressive disorder
• Postpartum depression
• Premenstrual dysphoric disorder
• Depressive episodes
• Anxiety disorders (Generalized, obsessive-compulsive, panic, post-traumatic stress, specific and social phobia)
• Eating disorders (Bulimia and anorexia nervosa)
• Pain disorder
• Other disorders: Sleepwalking disorder, childhood enuresis, nightmare disorder

Side Effects of TCAs

• Anticholinergic effects: dry mouth, constipation, urinary retention, blurred vision
• Cardiac effects: ECG changes, tachycardia, arrhythmias, orthostatic hypotension
• Endocrine and sexual effects: impotence, hyperprolactenemia, anorgasmia, amenorrhea, and ejaculatory disturbances
• Neurological effects: sedation, dizziness, drowsiness, tremors, myoclonic twitches of the tongue and upper extremities
• GIT: weight gain, nausea, vomiting

Name of TCAs

• Tofranil
• Anafranil
• Tryptizol
• Elavil
• Vivactil

Monoamine Oxidase Inhibitors (MAOIs)

• Monoamine(MA): norepinephrine, dopamine, serotonin (neurotransmitters), food, drug
• Monoamine Oxidase(MAO): enzyme responsible for metabolism of monoamine and tyramine (end metabolite of protein)
• Monoamine Oxidase Inhibitors(MAOI): Inhibit the effect of MAO enzyme inhibiting the metabolism of monoamine and tyramine.

Action of MAOIs

• These drugs inhibit monoamine oxidase (MAO) activity, metabolizing neurotransmitters (norepinephrine, dopamine, or serotonin) in synapses.
• This inhibition allows neurotransmitters to remain active longer in the brain, correcting a presumed deficit in monoamine function

Indications of MAOIs

• For patients who do not respond to TCAs
• Atypical depression (hyperphagia, hypersomnia, phobic anxiety)
• Acute depression (rapid action)
• Anxiety disorders (panic disorder, social phobia, generalized, obsessive-compulsive, post-traumatic stress)
• Bulimia nervosa

Side Effects of MAOIs

• Liver: hepato cellular damage, severe liver necrosis
• Psychotic: (retarded depression can convert to agitated depression)
• Hypomania
• Peripheral neuropathy
• Hypertensive crisis: (the "cheese effect")

Mechanism of Hypertensive Crisis

• Foods containing monoamines (aged cheese, beans, yeast products, smoked salmon, pickles, chocolate, coffee, chicken liver, bananas) are usually deactivated by MAO.
• When a person taking MAOIs consumes these foods, the monoamines accumulate, stimulating the sympathetic nervous system and increasing heart rate and blood pressure.
• This reaction can cause blood pressure to increase enough to induce intracranial bleeding or cardiovascular collapse.

Triggering factors for Hypertensive Crisis

• Foods containing tyramine are a trigger,
• Certain medications (cough mixtures, antipyretic, antitussive, antibiotics) contain ephedrine.

Symptoms of Hypertensive Crisis

• Blood pressure above 180/90
• Dilated pupils
• Severe occipital headache
• Stiff neck
• Nausea and vomiting
• Severe nosebleeds
• Tachycardia
• Chest pain, coma, death

Management of Hypertensive Crisis

• Preventive measures - Avoid foods or medications containing tyramine
• Curative measures - Stop the medication, administer antihypertensive, close monitoring of the patient

Name of MAOIs

• Nardil
• Parnate
• Marplan
• Emsam

Selective Serotonin Reuptake Inhibitors (SSRIs)

• Action of SSRIs: Inhibit the reuptake of 5HT by blocking reuptake sites, allowing 5HT to remain active, thereby correcting any deficit in its activity
• High safety margin (difference between toxic and therapeutic dose).

Indications of SSRIs

• Depression during pregnancy and postpartum
• Depression in elderly/medical patients with no cognitive/behavioral issues
• Major depressive disorder
• Anxiety disorders
• Eating disorders
• Chronic pain disorders

Side Effects of SSRIs

• Serotonin syndrome: Concurrent administration with MAOIs can raise plasma serotonin, causing a serious, fatal syndrome. Symptoms include: diarrhea, restlessness, agitation, hyperreflexia, fluctuations in vital signs, hyperthermia, shivering, rigidity, delirium, coma, and cardiovascular collapse
• Serotonin withdrawal: Symptoms from abruptly stopping SSRIs - dizziness, weakness, nausea, headache, rebound depression, and anxiety.
• Sexual dysfunction, nausea, vomiting, loss of appetite, indigestion, diarrhea, nervousness, insomnia, anxiety, drowsiness

Name of SSRIs

• Prozac
• Felozac
• Zoloft
• Cipram
• Celexa
• Cetalo

Post Selective Serotonin Reuptake Inhibitors

• Advantage: Rapid improvement, less side effects
• Disadvantage: Very expensive
• Action: Some drugs act like SSRIs inhibiting the reuptake of 5HT, increasing serotonin in the synapse. Some drugs act like tricyclic antidepressants but do not affect alpha, histamine, or ACh.

Names of Post Selective Serotonin Reuptake Inhibitors

• Effexor
• Trittico
• Trazodone

Why high suicide risk with antidepressant use:

• Antidepressants can improve mood before improving thought processes.
• Patients may experience increased energy leading to suicidal ideation.