Depression

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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.

• Likely cause inadequate monoamine levels
• Treatment
• Blocking NT reuptake by presynaptic end0

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Antidepressants

• Used to relieve symptoms of depression as well as
  help patients with anxiety disorders
• Major groups
• Tricyclic antidepressants
• Heterocyclic antidepressant
• Selective serotonin reuptake inhibitors
• Monoamine oxidase inhibitors
• Atypical antidepressants

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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)

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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).

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

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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.

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Antidepressant Mechanism
TCAs SSRIs Block Here
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TCA Side Effects

• Sedation
• Anticholinergic effects
• Orthostatic hypotension
• Cardiac toxicity
• Ventricular dysrythmias

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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.

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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.

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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

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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

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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

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MAOI Side Effects

• CNS Stimulation
• Anxiety, agitation
• Orthostatic hypotension
• Hypertensive Crisis
• From increased tyramine consumption
• Excessive arteriole constriction, stimulation of
  heart

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MAOI Dietary Tyramine
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Antidepressant Mechanism
TCAs SSRIs Block Here
16
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

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Antidepressants Agents

• TCAs
• imiprimine (Tofranil)
• amitriptyline (Elavil)
• nortriptyline (Pamelor )
• SSRIs
• fluoxetine (Prozac)
• paroxetine (Paxil)
• sertraline (Zoloft)
• Fluvoxamine

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

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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)

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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).

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

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Drugs for Bipolar Disorder

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

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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.

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Drugs for Bipolar DisorderLithium Interactions

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

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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

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

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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.

• Valproic acid (Depakene, Depakote)