Anti-depressants Dr. Sanjita Das

Range Tricyclics Tetracyclics Selective serotonin reuptake inhibitorsSelective serotonin reuptake inhibitors SSRI Serotonin norepinephrine reuptake inhibitorsSerotonin norepinephrine reuptake inhibitors SNRI MAOI Oddities Adjuvants

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

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.

Common TCA’s Amitriptyline Elavil Desipramine Norpramin, Doxepin Sinequan Imipramine Tofranil Nortriptyline Aventyl 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

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

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

SIDE EFFECTS OF TCA Anticholinergic effects CNS effects Endocrine and sexual side effects Decreased libido Weight gain- appetite stimulationcarbohy dratecraving Breast enlargement in both sexes 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

Tetracyclics 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

SSRI (Selective Serotonin Reuptake Inhibitors) 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.

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

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

Side Effects Common side effects GI nausea, diarrhea, weight loss Sexual dysfunction Headache Insomnia, nightmares Agitation, anxiety tremor Sweating 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

SSRI CitalopramFew interaction s Most expensive 20 mg /day Fluoxetine Prozac Sedation – Skin s/e Anxiety + Cheapest mg /day Fluvoxamin e Luvox Gut s/e +Insomnia -200 mg /day Paroxetine Paxil Sedation +Withdrawal problems ? 20 mg /day Sertraline Zoloft Diarrhoea50 mg /day

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.

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 MAOI The old ones block peripheral MAOI ( B ) and central MAOI (A) so a low tyramine diet is needed. ? Obsolete.

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

Side Effects MAOI’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 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

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

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

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