Chapter 16&17: Drugs for Depression and Mania

Question 1

What is major depressive disorder?

Answer 1

• It is a heterogeneous genetic disorder with onset at anytime of life.
• Is typically recurring
• Affects about 10% of the population.
• MDD will be the #1 health issue world-wide.

Question 2

What are the Symptoms of Major Depressive disorder?

Answer 2

**Emotional- **
Sad, Frustrated, Hopeless
Irritable
Apathetic

**Cognitive - **
Inappropriate Negative Thoughts and Ideas
Impaired

Neurovegetative
- Concentration, confusion, Pseudo Dementia
- Loss of Appetite
- Loss of Libido
- Loss of energy, lack of motivation
- loss of intrest in almost everything
- Neuroendocrine abnormalities, no diurnal rhythm
- Sleep disorder, REM advance and early morning awakening
- Cant experience of anticipate pleasure.

Question 3

In depressed patients what are the most common symptoms?

Answer 3

Question 4

What are Insulin Induced Hypoglycemic Convulsions?

Answer 4

Insulin-induced hypoglycemic convulsions were historically used as part of insulin coma therapy (ICT), a psychiatric treatment developed in the 1930s by Manfred Sakel for conditions like schizophrenia and severe depression. The therapy involved administering large doses of insulin to induce hypoglycemia, causing temporary comas or convulsions, with the belief that this “reset” brain function. Glucose was then administered to reverse the coma. While widely practiced mid-century, ICT was abandoned by the 1960s due to high risks, lack of evidence for efficacy, and the advent of safer, more effective treatments like antidepressants, antipsychotics, and electroconvulsive therapy (ECT).

Only used historically

Question 5

What are Electro-convulsive therapy?

Answer 5

Electroconvulsive Therapy (ECT) is a medical treatment for severe depression and other psychiatric conditions, particularly when other treatments like medication or psychotherapy have failed, or when rapid relief is needed, such as in cases of suicidal ideation or catatonia. ECT involves delivering controlled electrical currents to the brain under general anesthesia to induce a brief seizure, which is thought to alter brain chemistry and improve mood regulation. Typically administered in a series of 6–12 sessions, ECT is highly effective for treatment-resistant depression, with response rates of up to 90%. While it can cause temporary side effects like confusion and memory loss, modern ECT is a safe and effective option for alleviating severe depressive symptoms.

Currently safe and effective

Question 6

What is Monoamine Oxidase?

Answer 6

Mitochondrial enzyme that prevents buildup of Neuroactive Amines (Tyramine).

Question 7

What are the two types of MAO and what are their characteristics?

Answer 7

MAO-A

• Found in neurons, liver and GI tract.
• Highest Affinity for 5HT; less for NE/DA/Tyramine

MAO-B

• Found in nuerons, liver and platelets
• Highest affinity for Da; less for NE/5HT/Tyramine

Question 8

What is Tranylcypromine?

Dont neet to know just good to know.

Answer 8

**MAO Inhibitor **

• Non Selective for MAO-A and MAO-B
• Increased 5HT/NE in the Brain
• Increases absorption of Tyramine into the blood stream.

Question 9

What drug is this?

• Selective Inhibitor of MAO-A
• Increases 5HT/NE in the brain without affecting blood Tyramine.

Responsible for knowing.

Answer 9

Moclobemide

Question 9

Explain the Cheese-Wine reaction.

Answer 9

Question 10

What are some side effects of MAO Inhibitors?

Answer 10

Question 11

What is the mechanism and side effects of Tricyclic Antidepressants?

Answer 11

• Inhibit both NE and 5HT reuptake.
• Metabolites are more selective for NE creating a longer lasting NE effect after First Pass Metabolism
• Also block muscarinic and a1-andregenic receptors producing impaired memory, postural hypotension.

Metabolites have less affinity for muscarinic and a1 receptors.

Question 12

What are two common Tricyclic Antidepressants?

Answer 12

Imipramine - Inhibit 5HT and NE

Desipramine - Metabolite of Imipramine; selective for NE; Less affinity for A1 and Muscarinic receptors creating less side effects; can give this without Imipramine aswell.

Question 13

What is Venlafaxine?

Answer 13

5HT and NE reuptake inhibitor - Lack affinity for any NT receptors.

Question 14

What are the Selective Serotonin Reuptake inhibitors as what are their differences?

Inhibit only 5HT

Answer 14

Fluoxetine - Inhibits CYP P450 2D6- Problem with drug interactions with B-blockers and Narcotics.

Citalopram, Escitalopram - Less CYP P450 Drug interactions.

Question 15

How are Serotonin and NE Reuptake inhibitors involved with pain?

Answer 15

NE and 5HT have descending Pain inhibiting pathways through the spinal cord.

Reuptake inhibitors can enhance this and possibly be used to help pain.

Question 16

What are Atypical antidepressants?

Answer 16

Very heterogenous group of drugs that can have agonist, partial agonsit, antagonist, and/or reuptake inhibitory activity on 5HT/NE/Da neuromodulatory systems.

Question 17

What Atypical drug is this?

Apha 2 receptors in Pain pathways are inhibitory - Blocking these cause increased pain perception.

Answer 17

Mirtazapine

Question 18

What Atypical drug is this?

Answer 18

Trazodone

Question 19

What Atypical Drug is this?

Answer 19

Bupropion

A drug you might combien with SSRIs

Question 20

What are all the Atypical drugs?

Answer 20

• Mirtazapine
• Trazodone
• Bupropion

Question 21

Explain the Antidepressant mechanims.

Answer 21

• Drug effects are maximal within a few hours, however clinical improvement not seen for 2 to 6 weeks therefore the direct, acute drug action is not the therapeutic action of antidepressants.
• Down regulation of BARs (Beta Andregenic Receptors) is cmoon to anti-depresant interventions however it is unkown if this actually is the mechanism.
• Likely to be caused by BDNF (Brain neurotrophic Factor) - Some antidepressant can cause changes in epigentics to upregulate BDNF genes.

Question 22

What is Esketamine?

Answer 22

Approved by the FDA and Health Canada in treatment resistant depression.

Thought to have impact via and increase in BDNF and ites receptor TrkB

Rapic Acting within a few hours.

Question 23

What is Mania?

Answer 23

It is a stae of neurological abnormaility, where there is an elevated or irritable mood, arousal, and/or energy levels. Opposite to depression.

Question 24

What are the characteristics of Bipolar disorder?

Answer 24

• Affects 1-2% of the general population.
• Mood swings that cycle betwen depression and mania. Cycle varies from hours to years.
• Several different genes have been identified. - Onset at any time in life.

Question 25

What are the frequent symptoms in patients with mania?

Answer 25

Question 26

What are the treatment options for Bipolar and what are different characteristics?

Answer 26

Lithium

• Cornerstone Treatment - Can abort acute manic episode. Exerts mild antidepressant effect.
• Bad long term term as patients complain about side effects.
• Low Therapeutic Index - (0.6-1.2 meq/L vs 1.4 meq/L for toxicity)
• Interfers with receptor activated Phosphatidylinositol(All Metabotropic Receptor) Turnover
• Prevents Feedback inhibition of 5HT release through Antagonism.
• Enhances Glutamate Reuptake.

Carbamazepine

• Decreases voltage gated Na channels
• Potentiates GABA recptor currents.
• Exhibits antmanic, antidepressant, and prophylactic effects equivalent to lithium with fewer adverse effects in many patients.

Valproic Acid

• Decreases voltage-gated Na Channels
• Potentiates GABA receptor currents
• Additional effects as an histone deacetylase inhibitor (Epigenetics)
• Especially useful in patients with rapid cycling of manic and depressive episodes.
• Adverse Effects: Nausea, vomiting, diarrhea, headache..

Lamotrigine (Can help depression)

• Decreases voltage Gated Na Channels
• it also blocks, L, N, P type Ca channels (Ca channels involved in NT release). Weak 5HT receptor inhibition. **These throught to inhibit glutamate release in Limbic areas and cortex. - Mood Stabilizing effects. **
• Effective treatment of depressed phase of Bipolar Disorder where Na Blocking channel drugs are not.

Atypical Antipsychotics (Olanzapine, Risperidone, Aripiprazole)

• Approved for treatment of acute mania or mixed episodes.
• Antipsychotics may be required to suppress delusions and other psychotic sytoms accompanying mania.
• Combination Therapy: Olanzapine and Fluoxetine.
• Antidepressant Monotherapy May precipitate Mania

Question 27

What are the Treatment guidelines for Bipolar Disorder?

Answer 27

• 20-40% of patients do not respond to or tolerate lithium. - Then use the other 3 (Anticonvulsants)
• Atypical antipsychotics may be used for acute mania or mixed episodes.
• antidepressants may precipitate mania, and thus combination therapy of Olanzapine with Fluoxetine.