1. PHARMACOTHERAPY - I PHCY 310
University of Nizwa
College of Pharmacy and Nursing
School of Pharmacy
PHARMACOTHERAPY - I
PHCY 310
Lecture -11 Psychiatric Disorders “Depression” Dr. Sabin Thomas, M. Pharm. Ph. D. Assistant Professor in Pharmacy Practice School of Pharmacy University of Nizwa

2. Course Outcome
Upon completion of this lecture the students will be able to
Explain depression based on DCM-IV criteria,
Describe pathophysiology, non-pharmacological and pharmacological treatment for depression,
Individualize the treatments for depressive patients.

3. Depression is a mental disorder characterized by low mood, and by loss of interest or pleasure in normally enjoyable activities.

4. PATHOPHYSIOLOGY Biogenic amine hypothesis.
Depression may be caused by decreased brain levels of the neurotransmitters norepinephrine (NE), serotonin (5-HT), and dopamine (DA).
Postsynaptic changes in receptor sensitivity.
Changes in sensitivity of NE or 5-HT2 receptors may relate to onset of depression.

5. Therapeutic Choices
Pharmacologic Choices 1) Selective Serotonin Reuptake Inhibitors (SSRIs)
SSRIs are the first-choice antidepressants due to greater tolerability and ease of dosing.
Escitalopram, the stereoisomer of citalopram, has a similar side effect profile but superior efficacy to citalopram.
Paroxetine produces more extrapyramidal-type adverse effects than other SSRIs.
Fluoxetine has the longest half life as well as its active metabolite, desmethylflouxetine. So they have the advantage of reduced risk of discontinuation syndrome.
Sertraline doses shouldn’t exceed 150 mg/day for longer than 8 weeks to avoid overdose tachycardia.

6. 2) Dual Action Antidepressants
Bupropion, a norepinephrine and dopamine reuptake inhibitor, that is also considered a first-line agent for depression, and is also indicated for smoking cessation.
Trazodone is a (5HT2) receptor antagonist with weak serotonin reuptake inhibitory effects.
Trazodone causes severe hypotension and sedation due to blocking of α receptors, and H1 receptors respectively. So, it is prescribed at low doses (50–100 mg) as a hypnotic in combination with other antidepressants.

7. Mirtazapine (NaSSA) is also associated with sedation in addition to the problem of weight gain.
Venlafaxine (SNRI) requires cardiac monitoring because of cardiovascular toxicity (e.g. hypertension, tachycardia).
Duloxetine, another SNRI that has comparable efficacy to venlafaxine. Duloxetine is also indicated for neuropathic pain and for pain associated with fibromyalgia.
3) Tricyclic Antidepressants (TCAs)
TCAs are second–line antidepressants due to tolerability and safety concerns, especially cardiotoxicity following overdose.
Nortriptyline, a metabolite of amitriptyline, has been used to treat depression in elderly patients.
Clomipramine, the most serotonergic TCA, is favoured in the treatment of obsessive compulsive disorder.

8. Monoamine Oxidase Inhibitors (MAOIs)
Use of the irreversible (MAOIs) phenelzine and tranylcypromine carries the risk of fatal food and drug interactions (serotonin syndrome, hypertensive crisis).
Moclobemide is a reversible and selective MAO-A inhibitor that does not require the same dietary restrictions as irreversible MAOIs.
Moclobemide acts as an alternative 1st line antidepressant to SSRI or SNRI agents, while irreversible MAOIs are 3rd line agents for treating depression.

9. Other treatments:
1. Non-drug therapy: psychotherapy such as cognitive behavior therapy (CBT) is used in combination with antidepressants for severe major depression.
psychotherapy is the 1st line therapy of mild to moderate depression.
2. St John’s wort (Hypericum perforatum): they can only be used in the short term management of mild to moderate, but not severe depression.
3. Electroconvulsive therapy (ECT): although safe and
with a rapid antidepressant response, ECT is short lived and always requires an antidepressant to prevent relapse.