Anti-depressants

1. Anti-depressants Dr. Sanjita Das

2. Range • Tricyclics • Tetracyclics • Selective serotonin reuptake inhibitors SSRI • Serotonin norepinephrine reuptake inhibitorsSNRI • MAOI • Oddities • Adjuvants

3. Factors Influencing Choice • Features of illness, e.g. agitation, hypersomia • Suicide risk • Other therapy • Other illness. • Side effects • Cost • Special problems e.g. Age, driving, pregnancy

4. Drug Failure • Non compliance. • Inadequate dosage. • Other drugs e.g. alcohol, caffeine. • Unresolved outside problems. • Up to 25% failure even if above don’t apply.

5. Tricyclic Antidepressants Common TCA’s 􀂄 Amitriptyline Elavil 􀂄 Desipramine Norpramin, 􀂄 Doxepin Sinequan 􀂄 Imipramine Tofranil 􀂄 Nortriptyline Aventyl

6. Tricyclic Antidepressants Mechanism of action 􀂋 Block reuptake of norepinephrine and to lesser degree serotonin 􀂋 Block the muscarinic receptors that bind acetylcholine which leads to typical anticholinergic side effects

7. Amitryptyline Potent sedative Weight gain ++ Anticholinergic ++ 150mg / day (Therapeutic in 95% of adults) Clomipramine Similar side effects to amitryptyline. Said to be best for obsessional symptoms. 150mg / day Tricyclics

8. Dothiepin Sedative Same side effects as amitryptyline. By far and away the most toxic antidepressant. 150 mg / day Imipramine Stimulant Anticholinergic 150 mg/ day Tricyclics

9. Lofepramine Least toxic TCA. Minimal sedative side effects. Anticholinergic Doubts about efficacy. 210 mg / day Protriptyline Stimulant. Anticholinergic 40mg / day Tricyclics

10. SIDE EFFECTS OF TCA SERIOUS SIDE EFFECTS 􀂄 Cardiovascular 􀂋Hypotension 􀂋 Arrhythmias-tachycardia 􀂋ECG changes 􀂋Heart failure 􀂄 Baseline ECG should be done before starting treatment 􀂄 Contraindicated in cardiac disease 􀂄 Use cautiously with elderly 􀂄 Monitor vital signs regularly 􀂄 Anticholinergic effects 􀂄 CNS effects 􀂄 Endocrine and sexual side effects 􀂋Decreased libido 􀂋 Weight gain-appetite stimulationcarbohydratecraving 􀂋 Breast enlargement in both sexes

11. Maprotiline Similar side effect profile to amitryptyline. Seizures severe in overdose. 150 mg /day Mianserin Good safety in overdose. Few sedative or anticholinergic properties. Agranulocytosis risk 90 mg / day Tetracyclics

12. First choice in elderly. First choice if heart disease. First choice if suicide risk. More potent than cyclic drugs. Long half-life. Bigger therapeutic index and fewer side effects. More expensive. Side effects Like TCA reduce with time. Gut problems predominate. Flat dose response curve – so no need to titrate dose upwards. SSRI (Selective Serotonin Reuptake Inhibitors)

13. Mechanism of Action of SSRI’s 􀂄 Selective Serotonin Reuptake Inhibitors 􀂋 Selectively block reuptake of serotonin 􀂋 Do not block muscarinic receptors so they have little autonomic effects 􀂋 Safer than TCA’s and MAOI’s 􀂋No cardiac toxicity and not sedating

14. Indications For Use 􀂄 First line drug for all depression except severe inpatient depression 􀂄 Can be used much more safely with patients who have suicidal ideation 􀂄 Useful in treatment of depression that is accompanied by anxiety 􀂄 Also useful in many anxiety disorders

15. Side Effects Serious Side Effects SSRI’s 􀂄 Central Serotonin Syndrome 􀂋Caused by overaction of serotonin 􀂋 Most likely occurs when administered at same time as MAOI 􀂋 Should be at least 5 week time lag before changing to MAOI or 2 weeks before changing from MAOI to SSRI Common side effects 􀂄 GI nausea, diarrhea, weight loss 􀂄 Sexual dysfunction 􀂄 Headache 􀂄 Insomnia, nightmares 􀂄 Agitation, anxiety tremor 􀂄 Sweating

16. SSRI

17. SSNRI Venlafaxine • Selective Serotonin and noradrenaline reuptake inhibitor – like amitryptyline. • Few other effects – unlike amitryptyline. • Adverse effects: Dry mouth, somnolence, high BP, nausea, headache and dizziness.

18. MAOIThe old ones block peripheral MAOI ( B ) and central MAOI (A) so a low tyramine diet is needed. ? Obsolete. MECHANISM OF ACTION 􀂋 Interfere with this enzyme to destroy the monoamines norepinephrine, dopamine and serotonin 􀂋MAO present in liver cells to destroy the monoamine tyramine 􀂋Tyramine present in many foods 􀂋MAOI’s inhibit MAO in the liver and can result in fatal interactions between these drugs and tyramine rich foods 􀂋Tyramine triggers release of norepinephrine which is a powerful vasoconstrictor which can lead to hypertensive crisis

19. Indications for Use MAOI’s 􀂄 Responds best to atypical depression 􀂋 Overeating 􀂋 Phobic anxiety 􀂋 Panic attacks 􀂋Hypochondrias 􀂋 Chronic pain

20. Side Effects MAOI’s SERIOUS SIDE EFFECTS 􀂄 Hypertension 􀂄 Interaction with tyramine substances or with drugs containing epinephrine or psuedoephedrine can cause a life threatening hypertensive crisisIndications for Use MAOI’s 􀂄 Responds best to atypical depression 􀂋 Overeating 􀂋 Phobic anxiety 􀂋 Panic attacks 􀂋Hypochondrias 􀂋 Chronic pain Common Side Effects MAOI’s 􀂄 Weight gain 􀂄 Orthostatic hypotension 􀂄 Cardiac changes 􀂄 Other effects similar to TCA’s Common Side Effects MAOI’s 􀂄 Weight gain 􀂄 Orthostatic hypotension 􀂄 Cardiac changes 􀂄 Other effects similar to TCA’s SERIOUS SIDE EFFECTS 􀂄 Hypertension 􀂄 Interaction with tyramine substances or with drugs containing epinephrine or psuedoephedrine can cause a life threatening hypertensive crisis

21. Oddities Trazodone. • Unique structure. • Low cardiotoxicity, few anticholinergic side effects. • Drowsiness +Nausea.

22. Oddities Tryptophan • Natural amino acid - Serotonin precursor. • Eosinophilia-myalgia syndrome, Hospital initiation only. • Adjuvant to others ? Flupenthixol • Some doubts as to efficacy. • Fast action

23. Adjuvants and Combinations • Lithium, carbamazepine • Mixtures i.e. SSRI and TCA • Dangerous – need expert supervision