Types and groups of antidepressants
- 1. Types/Groups of Antidepressants Main Targets Indications Doses Mechanism of Action Side Effects Contraindications Tural Abdullayev
- 2. Selective Serotonin Reuptake Inhibitors (SSRIs)
- 3. Main targets • The serotonin transporter (SERT or 5-HTT)
- 4. Indications • Major depressive disorder • Anxiety Disorders (eg. Social anciety disorder) • Panic disorders • OCD • Eating disorders • Chronic stress • Post trauma (PTSD)
- 5. Doses • Escitalopram (least P450 Cytochrome inhibition) − Adult: 10–20 mg, once per day
- 6. Mechanism of Action • SSRIs inhibit the reuptake of serotonin • Repeated stimulation of post-synaptic cell • Chronic use − Pre-synaptic downregulation of synthesis − Post-synaptic downregulation of receptors
- 7. Side effects • Bone Fractures • Akathasia • Suicidal ideation (thoughts of suicide) • Photosensitivity • Sexual dysfunction
- 8. Contraindications • Combination may precipitate serotonin syndrome − Linezolid − Monoamine oxidase inhibitors (MAOIs) including moclobemide, phenelzine, tranylcypromine, selegiline and methylene blue − Lithium − Sibutramine − MDMA (ecstasy) − Dextromethorphan − Tramadol − Pethidine/meperidine − St. John's wort − Yohimbe − Tricyclic antidepressants (TCAs) − Serotonin-norepinephrine reuptake inhibitors (SNRIs) − Buspirone − Triptan − Mirtazapine • Reduce efficiency and GI bleeding − Aspirin − Ibuprofen • Use may precipitate Serotonine Syndrome: − High body temperature − Agitation − Increased reflexes − Tremor − Sweating − Dilated pupils − DIarrhea
- 10. Main targets • The serotonin transporter (SERT or 5-HTT) (Inhibition) • Norepinephrine transporter (NET) (Inhibition)
- 11. Indications • Major depressive disorder (MDD) • Posttraumatic stress disorder (PTSD) • Generalized anxiety disorder (GAD) • Social anxiety disorder (SAD) • Panic disorder • Neuropathic pain • Fibromyalgia • Chronic musculoskeletal pain
- 12. Doses • Venlafaxine – Immediate release: Initial dose: 37.5 mg orally twice a day or 25 mg orally 3 times a day Maintenance dose: May increase in daily increments of up to 75 mg orally at intervals of no less than 4 days Maximum dose: (moderately depressed outpatients): 225 mg orally per day Maximum dose (severely depressed inpatients): 375 mg orally per day – Extended release: Initial dose: 75 mg orally once a day Maintenance dose: May increase in daily increments of up to 75 mg orally at intervals of no less than 4 days Maximum dose (moderately depressed outpatients): 225 mg orally per day Maximum dose (severely depressed inpatients): 375 mg orally per day Use: Treatment of major depressive disorder (MDD)
- 13. Mechanism of Action • SNRIs inhibts reuptake of 5HT & NA • Increased concentration of substances • Continuing fiering of postsynaptic neruon
- 14. Side effects • Same as SSRIs including: – Loss of appetite – Weight-loss – Insomnia
- 15. Contraindications • Uncontrolled pre-existing hypertension • Chronic liver disease or alcoholism • Major eating disorders • Medications on previous slide
- 16. Serotonin Modulators and Stimulators (SMSs)
- 17. Main targets • Serotonin transporter (SERT or 5-HTT) • 5-HT1A-receptor (partial agonist) • 5-HT3-/ 5-HT7-receptors (antagonist)
- 18. Indications • Major depressive disorder
- 19. Doses • Vortioxetine – Adult: 5-20 mg per day as tolerated
- 20. Mechanism of Action • Modulation of serotonin receptors • Inhibition reuptake of serotonin (SRI-effect)
- 21. Side effects • Nausea • Diarrhea • Dry mouth • Constipation • Vomiting • Flatulence • Dizziness • Sexual dysfunction • Serotonine syndrome
- 22. Contraindications • Hypersensitivity to Vortioxetine • MAOIs use within 21 days (risk of Serotonin Syndrome)
- 23. Serotonin Antagonists and Reuptake Inhibitors (SARISs)
- 24. Main targets • 5-HT2A/2C serotoninergic receptors (antagonist) • 5-HT1A (partial agonist) • α1 & α2 adrenergic receptors (antagonist) • H1 histaminergic receptors (antagonist) • Higher doses: – The serotonin transporter (SERT or 5-HTT) (Inhibition)
- 25. Indications • Major depressive disorder • Anxiety disorders • Insomnia
- 26. Doses • Trazodone – Depression adult: 150-375mg once per day if extended-release tablet 10h
- 27. Side effects • Serotonine Syndrome • Cardiac arrhythmia • Priapism (continuous erection) • Hepatotoxicity • Elevated prolactin
- 28. Contraindications • According side effects • Also: – Hypersensitivity – Age under 18 as combination therapy (may cause suicidal ideation)
- 30. Main targets • Norepinephrine transporter (NET)
- 31. Indications • May be effective in treating depression in patients in whom SSRIs are ineffective • Sometimes effective in relieving physical symptoms of neuropathic pain such as diabetic peripheral neuropathy • Venlafaxine, desvenlafaxine, and duloxetine may precipitate a discontinuation syndrome if treatment is abruptly stopped.
- 32. Doses • Venlafaxine – Immediate release: Initial dose: 37.5 mg orally twice a day or 25 mg orally 3 times a day Maintenance dose: May increase in daily increments of up to 75 mg orally at intervals of no less than 4 days Maximum dose: (moderately depressed outpatients): 225 mg orally per day Maximum dose (severely depressed inpatients): 375 mg orally per day – Extended release: Initial dose: 75 mg orally once a day Maintenance dose: May increase in daily increments of up to 75 mg orally at intervals of no less than 4 days Maximum dose (moderately depressed outpatients): 225 mg orally per day Maximum dose (severely depressed inpatients): 375 mg orally per day Use: Treatment of major depressive disorder (MDD) • Duloxetine – Initial dose: 20 mg orally twice a day – Maintenance dose: 60 mg per day, given either once a day or as 30 mg orally twice a day – Maximum dose: 120 mg orally per day Use: Treatment of major depressive disorder (MDD)
- 33. Mechanism of Action • Venlafaxine, desvenlafaxine and duloxetine inhibit the reuptake of both serotonin and norepinephrine • Both SNRIs and TCAs, with their dual actions of inhibiting both serotonin and norepinephrine reuptake, are sometimes effective in relieving physical symptoms of neuropathic pain such as diabetic peripheral neuropathy. • SNRIs have little activity at adrenergic, muscarinic, or histamine receptors. • Venlafaxine – Potent inhibitor of serotonin reuptake – At medium to higher doses, is an inhibitor of norepinephrine reuptake. – At high doses is an mild inhibitor of dopamine reuptake. – Has minimal inhibition of the CYP450 isoenzymes and is a substrate of the CYP2D6 isoenzyme. • Duloxetine – inhibits serotonin and norepinephrine reuptake at all doses. – Moderate inhibitor of CYP2D6 and CYP3A4 isoenzymes.
- 34. Side effects • Venlafaxine – Nausea – Headache – Sexual dysfunction – Dizziness – Insomnia – Sedation – Constipation – At high doses: increase in blood pressure and heart rate • Duloxetine – GI side effects are common including nausea, dry mouth, and constipation. Diarrhea and vomiting are seen less often. – Insomnia, – Dizziness – Somnolence – Sweating – Sexual dysfunction – Possible risk for an increase in either blood pressure or heart rate.
- 35. Contraindications • Duloxetine – Should not be administered to patients with hepatic insufficiency. • Velnafaxine – Starting Venlafaxine tablets in a patient who is being treated with MAOIs such as linezolid or intravenous methylene blue is also contraindicated because of an increased risk of serotonin syndrome
- 37. Main targets • Serotonergic receptors • α-adrenergic receptors • Histaminic receptors • Muscarinic receptors • Amoxapine also blocks 5-HT2 and D2 receptors.
- 38. Indications • The TCAs are effective in treating moderate to severe depression. • Some patients with panic disorder also respond to TCAs. • Imipramine has been used to control bed-wetting in children (older than age 6 years) by causing contraction of the internal sphincter of the bladder. • Amitriptyline, – have been used to treat migraine headache and chronic pain syndromes (for example, neuropathic pain) in a number of conditions for which the cause of the pain is unclear. • Low doses of TCAs, especially doxepin, can be used to treat insomnia.
- 39. Doses • Amitriptyline Usual Adult Dose for Depression 75 – 100 mg orally per day in divided doses; this may be increased to a total of 150 mg per day if needed Maintenance dose: 40 to 100 mg orally as a single dose at bedtime Usual Geriatric Dose for Depression 10 mg orally 3 times a day with 20 mg at bedtime Usual Pediatric Dose for Depression (12 yrs or older) 10 mg orally 3 times a day with 20 mg at bedtime • Desipramine Usual Adult Dose for Depression – 100 to 200 mg orally per day (max. 300mg ) Usual Geriatric Dose for Depression – 25 to 100 mg orally per day (max. 150mg)
- 40. Mechanism of Action 1. Inhibition of neurotransmitter reuptake: • TCAs and Amoxapine are – potent inhibitors of the neuronal reuptake of norepinephrine and serotonin into presynaptic nerve terminals. – At therapeutic concentrations, they do not block dopamine transporters. – By blocking the major route of neurotransmitter removal, the TCAs cause increased concentrations of monoamines in the synaptic cleft, ultimately resulting in antidepressant effects. – Maprotiline and desipramine are relatively selective inhibitors of norepinephrine reuptake. 2. Blocking of receptors: • TCAs also block serotonergic, α-adrenergic, histaminic, and muscarinic receptors • Actions at these receptors are likely responsible for many of the adverse effects of the TCAs. • Amoxapine also blocks 5-HT2 and D2 receptors.
- 41. Side effects • Blockade of muscarinic receptors: – Blurred vision – Xerostomia(dry mouth) – Urinary retention – Sinus tachycardia – Constipation – Aggravation of narrow-angle glaucoma • Blockage α-adrenergic receptors: – Orthostatic hypotension (imipramine is the most likely cause) – Dizziness – Reflex tachycardia • Sedation – may be prominent, especially during the first several weeks of treatment • Weight gain – is a common side effect • Sexual dysfunction – Erectile dysfunction in men – Anorgasmia in women – incidence is still considered to be lower than the incidence of sexual dysfunction associated with the SSRIs
- 42. Contraindications • TCAs (like all antidepressants) should be used with caution in patients with bipolar disorder, even during their depressed state, because antidepressants may cause a switch to manic behavior • Depressed patients who are suicidal should be given only limited quantities of these drugs and be monitored closely. • The TCAs may exacerbate certain medical conditions, such as unstable angina, benign prostatic hyperplasia, epilepsy, and preexisting arrhythmias. Caution should be exercised with their use in very young or very old patients as well.
- 44. Main targets • Adrenergic receptors • 5-HT receptors • Dopamine receptors
- 45. Indications • Amoxapine – Indicated for the relief of symptoms of depression in patients with neurotic or reactive depressive disorders as well as endogenous and psychotic depressions – Indicated for depression accompanied by anxiety or agitation • Maprotiline – Depressive illness in patients with depressive neurosis (dysthymic disorder) and manic depressive illness, depressed type (major depressive disorder) – It’s also effective for the relief of anxiety associated with depression. • Mirtazapine – Indicated for the treatment of major depressive disorder
- 46. Doses • Amoxapine – Usual Adult Dose for Depression • Initial dose: 50 mg orally two or three times a day • Maintenance dose: 100 mg orally two or three times a day • Maximum dose: 600 mg orally per day – Usual Geriatric Dose for Depression • Initial dose: 25 mg orally two or three times a day • Maintenance dose: 50 mg orally two or three times a day • Maximum dose: 300 mg orally per day • Maprotiline – Usual Adult Dose for Depression • Initial dose: 75 mg orally once a day or in divided doses • Maintenance dose: 75 to 150 mg/day • Maximum dose: 225 mg/day – Usual Geriatric Dose for Depression • Initial dose: 25 mg orally once a day or in divided doses • Maintenance dose: 50 to 75 mg/day • Mirtazapine – Usual Adult Dose for Depression • Initial dose: 15 mg orally once a day at bedtime • Maintenance dose: 15 to 45 mg orally once a day • Maximum dose: 45 mg/day
- 47. Mechanism of Action • Reduce the uptake of norepinephrine and serotonin and blocked the response of dopamine receptors to dopamine.
- 48. Side effects • Amoxapine – Drowsiness – Dry mouth – Constipation – Blurred vision • Mirtazapine – Somnolence – Dry mouth – Constipation – Increased appetite – Weight gain • Maprotiline – Dry mouth – Constipation – Drowsiness – Nervousness – Anxiety – Insomnia – Agitation
- 49. Contraindications • Amoxapine – Contraindicated in patients hypersensitive to dibenzoxazepine compounds. – Should not be given concomitantly with monoamine oxidase inhibitors (Hyperpyretic crises, severe convulsions, and deaths have occurred in patients receiving tricyclic antidepressants and monoamine oxidase inhibitors simultaneously) • Mirtazapine – Contraindicated in patients with a known hypersensitivity to mirtazapine or to any of the excipients. – in a patient who is being treated with MAOIs such as linezolid or intravenous methylene blue is also contraindicated because of an increased risk of serotonin syndrome • Maprotiline – Contraindicated in patients hypersensitive to Maprotiline and in patients with known or suspected seizure disorders. – Should not be given concomitantly with monoamine oxidase (MAO) inhibitors – Not recommended for use during the acute phase of myocardial infarction.
- 51. Main targets • Monoamine oxidase (MAO) – mitochondrial enzyme
- 52. Indications • Phenelzine – Effective in depressed patients clinically characterized as "atypical," "nonendogenous," or "neurotic." • Tranylcypromine – Major Depressive Episode Without Melancholia • Isocarboxazid – Treatment of depression
- 53. Doses • Phenelzine – Usual Adult Dose for Depression: • Initial dose: 15 mg, orally, 3 times a day • Early phase treatment: Increase to at least 60 mg per day fairly rapidly, as tolerated -90 mg per day may be needed for sufficient MAO inhibition -Clinical response may not be seen until at least 4 weeks at 60 mg per day dosing • Maintenance dose: After maximal benefit is achieved, reduce dose slowly over several weeks. • Tranylcypromine – Usual Adult Dose for Depression: • Usual effective dose: 30 mg per day, orally, in divided doses (max. 60mg) • Isocarboxazid – Usual Adult Dose for Depression: • Initial dose: 10 mg, orally, 2 times a day (max. 60 mg, divided into 2 to 4 doses per day)
- 54. Mechanism of Action • Most MAOIs, such as phenelzine, form stable complexes with the enzyme, causing irreversible inactivation. – This results in increased stores of norepinephrine, serotonin, and dopamine within the neuron and subsequent diffusion of excess neurotransmitter into the synaptic space • These drugs inhibit not only MAO in the brain, but also MAO in the liver and gut that catalyze oxidative deamination of drugs and potentially toxic substances, such as tyramine, which is found in certain foods. The MAOIs, therefore, show a high incidence of drug- drug and drug-food interactions. • Although MAO is fully inhibited after several days of treatment, the antidepressant action of the MAOIs, like that of the SSRIs and TCAs, is delayed several weeks.
- 55. Side effects • Phenelzine – Most important adverse event reported is hypertensive crisis, which has been associated with intracranial bleeding and has been fatal. • Tranylcypromine – The most important adverse event is hypertensive crisis, which may be fatal. The most common adverse event is insomnia, which can frequently be overcome by giving the last dose of the day no later than 3 pm or reducing dosage • Isocarboxazid – Disturbances in cardiac rhythm – Hypertensive crisis – Dizziness – Headache – Blurred vision – Nausea – Dry mouth – Hallucinations have been reported with high doses
- 56. Contraindications • Phenelzine – Should not be used in patients who are hypersensitive to the drug or its ingredients, with pheochromocytoma, congestive heart failure, severe renal impairment or renal disease, a history of liver disease, or abnormal liver function tests. – Phenelzine sulfate should not be used in combination with dextromethorphan or with CNS depressants such as alcohol and certain narcotics. – Phenelzine sulfate should not be administered together with or in rapid succession to other MAO inhibitors because HYPERTENSIVE CRISES and convulsive seizures, fever, marked sweating, excitation, delirium, tremor, coma, and circulatory collapse may occur. • Tranylcypromine – In patients with cerebrovascular defects or cardiovascular disorders – In the presence of pheochromocytoma – In combination with MAO inhibitors or with dibenzazepine-related entities • Isocarboxazid – Hypersensitivity to isocarboxazid or any component of the formulation; cardiovascular disease (including hypertension); cerebrovascular defect (suspected or confirmed); history of headache; history of hepatic disease or abnormal liver function tests; pheochromocytoma; severe renal impairment