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Depression

At least 5 of the following symptoms for 2 weeks (criteria 1 or 2 essential): 1. Depressed mood. 2. Loss of interest or pleasure. 3. Significant weight loss or gain. 4. Insomnia or hypersomnia. 5. Psychomotor agitation or retardation. 6. Fatigue or loss of energy. 7. Feelings of worthlessness or excessive guilt. 8. Impaired thinking or concentration; indecisiveness. 9. Suicidal thoughts/thoughts of death.

Depression
Likely cause: inadequate monoamine levels Treatment :
Blocking NT reuptake by presynaptic end

Antidepressants
Used to relieve symptoms of depression as well as help patients with anxiety disorders Major groups:
1) 2) 3) 4) 5) Tricyclic antidepressants Heterocyclic antidepressant Selective serotonin reuptake inhibitors Monoamine oxidase inhibitors Atypical antidepressants

Antidepressants
They now have recognised roles in the treatment of generalized anxiety disorder, panic disorder, obsessive compulsive disorder, social phobia, bulimia nervosa, chronic pain and Nocturnal enuresis (Imipramine)

Antidepressants
On balance, the selective serotonin reuptake inhibitors (SSRIs) and other newer antidepressants may be better tolerated and have a wider safety margin than the tricyclic antidepressants (TCAs) and irreversible nonselective monoamine oxidase inhibitors (MAOIs).

Antidepressants
A delay in onset of antidepressant response of at least 1 to 2 weeks occurs with all antidepressants.

Antidepressants
Tricyclic Antidepressants (TCAs):
Prototype = Imipramine Mechanism of Action:
Block neuronal reuptake of norepinephrine and serotonin which intensifies their effects Uses: Depression, bipolar disorder, Considerations: Initial responses develop in 1-3 weeks; maximal responses over 1 to 2 months.

Antidepressant Mechanism
TCAs & SSRIs Block Here

TCA Side Effects


Sedation Anticholinergic effects Orthostatic hypotension Cardiac toxicity
Ventricular dysrythmias

Heterocyclic antidepressant
Second generation antidepressant (e.g., Amoxapine, bupropion, maprotiline, trazodone) and newer, third generation drugs (duloxetine, mirtazapine, nefazodone, venlafaxine). It has less cardiovascular and anticholinergic adverse effects than the TCAs and has a wider margin of safety in overdose.

Antidepressants
Selective Serotonin Reuptake Inhibitors (SSRIs):
Most commonly prescribed group of antidepressants As effective as TCAs but do not cause hypotension, sedation, or anticholinergic effects (dry mouth, blurred vision, photophobia, constipation, urinary hesitancy, tachycardia). Use: major depression/ Prototype = Fluoxetine (Prozac) Mechanism of action:
Produces selective inhibition of serotonin reuptake Blockade of transmitter uptake occurs quickly, therapeutic effects are the result of adaptive cellular changes that take place in response to prolonged uptake blockade

Other SSRIs: citalopram, fluvoxamine, paroxetine and sertraline.

Selective Serotonin Reuptake Inhibitors (SSRIs)


Block only serotonin (not NE) reuptake
Elevate serotonin levels

Fewer side effects than TCS


No hypotension No anticholinergic effects No cardiotoxicity

Most common side effect


Nausea, diarrhoea, insomnia, sexual dysfunction

Antidepressants
Monoamine Oxidase Inhibitors (MAOIs):
Most dangerous: risk of triggering hypertensive crisis by eating foods rich in tyramine. MAO is an enzyme found in the liver, the intestinal wall, and terminals of monoamine-containing neurons. Their function is to convert NE, serotonin, and dopamine into inactive products. MAO inhibitors block this process. Uses: depression, bulimia, obsessive-compulsive disorder, reduce panic attacks Caution: many drug interactions

Monoamine Oxidase Inhibitors (MAOIs)


Monoamine oxidase
Present in liver, intestines & MonoAmin releasing neurons Inactivates monoamines Inactivates dietary tyramine in liver
Foods rich in tyramine: cheese & red wine

MAOI Side Effects


CNS Stimulation
Anxiety, agitation

Orthostatic hypotension Hypertensive Crisis


From increased tyramine consumption
Excessive arteriole constriction, stimulation of heart

MAOI & Dietary Tyramine

Antidepressant Mechanism
TCAs & SSRIs Block Here

Antidepressants
Atypical Antidepressants:
Bupropion (Wellbutrin) Bupropion is an antidepressant which inhibits neuronal reuptake of dopamine and is a noncompetitive nicotine antagonist at nicotinic cholinergic receptors.
Adverse effects include nausea, rashes, facial swelling, insomnia and dry mouth. Contraindicated in patients with a seizure disorder; bulimia or anorexia nervosa; monoamine oxidase inhibitor treatment in the previous 14 days

Antidepressants Agents
TCAs
imiprimine (Tofranil) amitriptyline (Elavil) nortriptyline (Pamelor )

MAOIs
phenelzine (Nardil) Moclobemide Second generation antidepressant (eg, Amoxapine, bupropion, maprotiline, trazodine and newer, third generation drugs (duloxetine, mirtazapine, nefazodone, venlafaxine).

SSRIs
fluoxetine (Prozac) paroxetine (Paxil) sertraline (Zoloft) Fluvoxamine

Drugs for Bipolar Disorder


Bipolar Disorder:
Severe biologic illness characterized by recurrent fluctuations in mood; either the mood is abnormally elevated or depressed. Drug therapy:
Mood stabilizers Antidepressants (used w/mood stabilizer) Antipsychotics (used w/mood stabilizer)

Drugs for Bipolar Disorder


Mood Stabilizing Drugs:
Provide relief from an acute manic or depressive episode, preventing symptoms from recurring. Prototype: Lithium
Low therapeutic index so levels MUST be monitored (toxicity can occur at blood levels that are only slightly greater than therapeutic).

Drugs for Bipolar Disorder


Prototype: Lithium Action Specific mechanism unknown; alters sodium transport in nerve and muscle cells

Drugs for Bipolar Disorder


Prototype: Lithium CV: Arrhythmias; hypotension; peripheral circulatory collapse. CNS: Tremor; ataxia; dizziness; confusion; hallucinations; seizures; drowsiness; muscular weakness; slurred speech.

Drugs for Bipolar Disorder


Prototype: Lithium EENT: Blurred vision; tinnitus. GI: Anorexia; nausea; vomiting; diarrhea; sialorrhea; dry mouth; parotitis. GU: Urinary urgency; polyuria; albuminuria; sexual dysfunction; symptoms of nephrogenic diabetes; decreased creatinine clearance.

Drugs for Bipolar Disorder Lithium Interactions


Acetazolamide, osmotic diuretics, theophyllines, urinary alkalinizers: Increased renal excretion of lithium. ACE inhibitors, thiazide diuretics, loop diuretics, NSAIDs, fluoxetine : Increased lithium serum levels.

Drugs for Bipolar Disorder


Mood Stabilizing Anticonvulsants:
Prototype = Valproic acid (Depakene, Depakote)
It is the only antiseizure agent that has been approved by the FDA for treatment of BPD. It is as effective as lithium, works faster, and has a higher therapeutic index and more desirable side effect profile. First line treatment for BPD

Drugs for Bipolar Disorder


Valproic acid (Depakene, Depakote) Action Believed to work by increasing brain levels of GABA. It may also inhibit catabolism of GABA, potentiate postsynaptic GABA responses, and affect potassium channels or directly stabilize membranes.

Drugs for Bipolar Disorder


Valproic acid (Depakene, Depakote) Contraindications Hepatic disease dysfunction.

Drugs for Bipolar Disorder


Valproic acid (Depakene, Depakote)