1. Anti-depressants Depression is considered to be due to functional deficit of neurotransmitters like norepinephrine and / or serotonin. Antidepressants act by increasing the concentration of neurotransmitters norepinephrine and / or serotonin in the brain.

2. Anti-depressants Drugs used in depression are : Tricyclic Antidepressants (TCA). Selective Serotonin Reuptake Inhibitors (SSRI). Atypical Antidepressants. MAO-A inhibitors.

3. Anti-depressants TCA : NE / 5-HT reuptake inhibitors : Tertiary amines : Block reuptake of 5-HT (serotonin) to a greater extent than NE. Amitriptyline, Imipramine, Clomipramine Secondary amines : Block the reuptake of NE more than serotonin. Desipramine, Nortriptyline, Amoxapine

4. Anti-depressants TCA

5. Anti-depressants Adverse effects of TCA : Antimuscarinic effects – dry mouth, blurred vision and urinary retention. Alpha-1 blocker – Hypotension. Histamine -1 blocker – Weight gain. Arrhythmia. Seizures. Induction of mania.

6. Anti-depressants TCA TCA block α-1, muscarinic and histamine -1 receptors.

7. Anti-depressants TCA SedationAntimuscarinic Hypotension Imipramine (Tofranil) ++ +++ Clomipramine (Anafranil) +++ Amitriptyline (Elavil) +++ Desipramine (Norpramin) + + + Nortriptyline (Pamelor) + + + Amoxapine* (Ascendin) + + +

8. Anti-depressants Drug interactions of TCA : Hypertensive crises when given with MAO Inhibitors. Serotonin syndrome with SSRI and MAO Inhibitors.

9. Anti-depressants SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRI): Fluoxetine (Prozac) Fluvoxamine (Luvox) Sertraline (Zoloft) Paroxetine (Paxil) Citalopram (Celexa) Escitalopram (Lexapro)

11. SSRI GI effectsSexual effectsAgitation Fluoxetine (Prozac) +++++ Sertraline (Zoloft) +++ + Paroxetine (Paxil) ++++++/- Fluvoxamine (Luvox) ++++++/- Citalopram (Celexa) ++++++/- Escitalopram (Lexapro) ++++++/-

12. Anti-depressants Adverse effects of SSRI: Nausea. Insomnia. Sexual dysfunction. Suicidal ideation Weight loss initially but regained after 12 months. Induction of mania/hypomania.

13. Anti-depressants Drug Interactions of SSRI: Most SSRI are inhibitors of cytochrome P 450 and can ↑ levels of TCA. One major contraindication of SSRI is the concomitant use of MAOI. This is likely to cause severe serotonin syndrome. Serotonin syndrome characterized by restlessness, tremor, myoclonus, ↑↑ temperature and death.

14. Anti-depressants SEROTONIN / NOR EPINEPHRINE REUPTAKE INHIBITORS : (SNRI): Venlafaxine (Effexor): It is a serotonin and NE reuptake inhibitor in a dose dependent manner. It does not block muscarinic, adrenergic, or histaminic receptors. It is used for the treatment of depression and anxiety disorders. Adverse effects includes nausea, sexual dysfunction, hypertension, suicidal thoughts.

15. Anti-depressants SEROTONIN / NOR EPINEPHRINE REUPTAKE INHIBITORS : ( SNRI ) : Duloxetine (Cymbalta): Used in major depression, anxiety and also diabetic neuropathic pain. It causes nausea and ↑ risk of suicide.

16. Anti-depressants ATYPICAL ANTIDEPRESSANTS: Bupropion (Wellbutrin): It is an inhibitor of reuptake of NE and dopamine. Used in ADHD and adjunct therapy for cessation of smoking. No weight gain and sexual dysfunction Very less risk for “switching” to mania/hypomania. It causes seizures at high dose.

17. Anti-depressants ATYPICAL ANTIDEPRESSANTS: Mirtazapine (Remeron) : It enhances the noradrenergic transmission by blocking presynaptic α - 2 receptors It is a potent anti-histaminic with greater sedating effects and weight gain.

18. Anti-depressants ATYPICAL ANTIDEPRESSANTS: Trazodone (Desyrel), Nefazodone (Serzone) These act mainly by blocking 5-HT-2A receptors. Trazodone causes sedation and priapism. Nefazodone can cause serious hepatic injury.

19. Anti-depressants MAO INHIBITORS : Phenelzine (Nardil), Tranylcypromine (Parnate), Moclobemide. MAO inhibitors are useful in atypical depression. MAO-A inhibitors are used when all other antidepressants are not useful and ECT refused.

20. MAO-Inhibitors

21. Anti-depressants MAO INHIBITORS : Adverse effects : Phenelzine, Tranylcypromine The most common adverse effects of MAO inhibitors is postural hypotension. Anti-cholinergic side effects like dry mouth are less common compared with TCA. Impotence and anorgasmia are noted with MAO inhibitors.

22. Anti-depressants MAO INHIBITORS: Interactions: MAO Inhibitors interact with tyramine – dangerously leading to hypertensive crisis – cheese reaction. Avoid Cheese, Wine, Beer, Pickled fish, Brewer’s yeast, Fava beans, Beef, Chicken liver. Avoid sympathomimmetic drugs like phenylephrine.

23. Anti-depressants Selegiline (Emsam): It is the first MAO inhibitor in transdermal patch form used for major depression. It can be used without the dangers of dietary interactions associated with oral MAOI. St. John’s Wort : This herbal medication is effective and safe for mild or moderate depression. The active ingredient is hypercium. It inhibits MAO and also appears to block the reuptake of serotonin.

24. Anti-depressants Anti-depressant effect seen after 2-4 weeks

25. Anti-depressants Uses of Antidepressants: Enuresis – TCA ADHD – TCA Anxiety disorders like panic / phobia and bulimia nervosa – SSRI OCD – SSRI / Clomipramine Neuropathic pain – TCA

26. Seizures Hypotensi on Anticholi nergic Sedation Cardiac effects Sexual effects TCA+++ SSRI+-- Insomnia -+++ Bupro pion ++-- Psychosis -- MAOI++++++ Insomnia -+++

27. Anti-depressants Conclusions: SSRIs are safe and effective for the treatment of major depression. SSRIs are first line for chronic treatment of anxiety disorders including OCD. MAO inhibitors are effective for the treatment of atypical depression. Psychotic depressed patients usually requires ECT.

30. Bipolar disorder

31. Mood stabilizers LITHIUM is a monovalent cation Lithium has a narrow therapeutic index Lithium is used for prevention and the treatment of bipolar disorder. Valproate and carbamazepine are the alternatives for the BPD. Lamotrigine also acts as a mood stabilizer.

32. Mood stabilizers MECHANISM OF ACTION: LITHIUM Inhibits inositol monophosphatase and thus interfere with phosphatidyl inositol pathways Decrease the recycling of inositol in the neuronal cell membrane. Decrease the cAMP.

34. Mood stabilizers PHARMACOKINETICS OF LITHIUM: Orally absorbed. Slow onset. Plasma levels ~ 1 meq / liter. Thiazides, NSAIDS enhances lithium toxicity.

35. Mood stabilizers Adverse effects of Lithium : Tremors, weight gain, acne. Polyuria and polydipsia – nephrogenic diabetes insipidus – Amiloride. Hypothyroidism. Seizures and arrhythmia. Teratogenicity - Ebstein’s malformation.

36. Mood stabilizers Symbyax is a combination of olanzapine and fluoxetine for the treatment of bipolar depression. Aripiprazole (Abilify) is approved for the treatment of acute manic and mixed episodes associated with bipolar disorder.