M5: Drugs For the Affective Disorders

Question 1

Affective Mood Disorders

Answer 1

Group of conditions where the main feature is disturbances in the person’s mood

Classification:
- Depressive disorders – e.g., MDD
- Bipolar disorders
- Anxiety disorders
- Substance-induced
- Secondary to general medical condition

Question 2

Pathophysiology of Depression

Answer 2

1. Neurotrophic Hypothesis:
   - Loss of neurotrophic support
   - Decrease BDNF
2. Monoamine Hypothesis:
   - Decrease amount OR function of cortical & limbic monoamines (5-HT, NE, DA)
3. Amine Hypothesis

Question 3

Treatment of Depression

Answer 3

1. Modification of lifestyle
2. Psychotherapy
3. Pharmacotherapy – antidepressants

Question 4

(7) Antidepressants

Answer 4

1. Selective Serotonin Reuptake Inhibitors (SSRIs)
2. Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)
3. Tricyclic Antidepressants (TCAs)
4. 5-HT Receptor Antagonists / Modulators
5. Norepinephrine-Dopamine Reuptake Inhibitors (NDRIs)
6. Monoamine Oxidase Inhibitors (MAOIs)
7. Tetracyclic Antidepressants (TeCAs) – (NaSSA)

Question 5

Antidepressants: General Considerations

Answer 5

First line treatment: SSRI, SNRI, NDRI, or NaSSA

MAOIs Drug Interactions:
- SSRIs, SNRIs, TCAs serotonin syndrome
- Tyramine containing food malignant hypertension CVS or AMI

M-cpp:
- Major active metabolite of trazodone
- Non-selective serotonin receptor modulator
- Serotonin releasing agent

Question 6

Bipolar Disorder

Answer 6

• Was known as manic-depressive disorder
• Distinct from but share some similarities with schizophrenia
• Phases: manic – hypomanic – depressive
• Treatment:
  1. Depressive Periods:
• Antidepressants

2. Manic Periods:
   - Antipsychotics
   - Lithium
   - Anticonvulsants

Question 7

LITHIUM
- Mechanism of Action
- Pharmacokinetics
- Adverse Effects

Answer 7

• Small monovalent cation (Li+)
• First used in the mid-19th century to treat gout
  1949, used to treat bipolar disorder – manic phase

Other indications:
- Recurrent depression
- Acute major depression
- Both combined with antidepressant
- Schizophrenia (combined with an antipsychotic)

MECHANISM OF ACTION:
1. Not clearly understood – acts on multiple levels

2. Effects on Electrolytes & Ion Channels:
   - Can substitute for Na+ in generating action potential
3. Effects on 2nd Messengers:
   - Decrease formation of IP3 & DAG
   - Decrease NE-sensitive AC
4. Effects on Neurotransmitters:
   - Decrease DA & NMDA receptors
   - Increase GABA receptors

PHARMACOKINETICS:
1. Absorption: 6-8hours, peak plasma levels in 30minutes to 2 hours

2. Distribution: slow entry into intracellular, from 0.5L/kg into 0.7-0.9L/kg. No protein binding
3. Metabolism: none
4. Excretion:
   - entirely in urine
   - plasma half life about 20 hours
5. Target Plasma Concentration: 0.6-1.4 mEq/L
6. Dosage: 0.5mEq/kg/d in divided doses

A safe blood level of lithium is 0.6 and 1.2 milliequivalents per liter (mEq/L). Lithium toxicity can happen when this level reaches 1.5 mEq/L or higher. Severe lithium toxicity happens at a level of 2.0 mEq/L and above, which can be life-threatening in rare cases

ADVERSE EFFECTS:
LITHIUM:
L. eukocytosis
I. nsipidus (nephrogenic diabetes insipidus)
T. remors – Teratogenic effect
H. ypothyroidism
I. ncreased body weight (? edema due to Na+ retention)
U. nhungry (anorexia)
M. otor hyperactivity (+ ataxia, aphasia, dysarthria)

Question 8

Anticonvulsants and Bipolar Disorder

Answer 8

DRUGS = Valproic acid, Carbamazepine, Lamotrigine

Now more commonly prescribed than lithium

Have mood-stabilizing properties

Originally used to treat epilepsy

Mechanism in bipolar disorder: unclear! (as antiepileptics, carbamazepine & lamotrigine are Na+ channel blockers)

Absorption: GI

Administration: oral