Anti depressant Drugs
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Anti depressant Drugs Rezaei M. MD Psychiatrist Tricyclics Tertiary amines: Imipiramine Amitriptyline Clomipramine Trimipiramine Doxepin Secondary amines Desipiramine Nortriptyline protriptyline Tetracyclics Amoxapine Maprotiline Minaserin Pharmacological actions Absorbed from oral administration Peak plasma concentration 2-8 hrs Half life vary from 10 to 70 hrs ( nortriptyline, maprotiline and protriptyline may have longer half lives ) 5-7 days are needed to reach steady state plasma concentration Metabolized in liver by cytochrome p-450 enzyme Drug interaction with quinidine, cimetidine , fluxetine, serteraline, paroxetine , phenothiazine, carbamazepine Genetic variability between persons are responsible for up to 40-fold differences in plasma concentrations of TCA`s Mechanism of action: Block the reuptake of NEP and serotonin Competitive antagonists at the muscarinic acetylcholine, histamine H1, @1 and @2-adrenergic receptors.( Amoxapine, nortriptyline, desipramine, maprotiline have the least anticholinergic activity. Doxepine has the most antihistaminergic activity, clomipramine is the most sertonin-selective of the TCAs) Adverse effects Psychiatric effects A major adverse effect is the possibility of inducing a manic episode in patients +/- history of BMD I disorder Anticholinergic effects Patient may develop a tolerance for these effects with continued treatment. Amitriptyline Imipramine Doxepin Trimipramine Dry mouth, constipation, blurred vision , urinary retention, Treatment Beware of narrow angle glaucoma Severe reactions may induce CNS anticholinergic syndrome with confusion and delirium Sedation Amitriptyline Trimipramine Doxepin The least sedative effects are in desipiramine and protriptyline Autonomic effects Orthostatic HOTN ,Partly because of @1-adrenergic blockade Nortriptyline least likely cause the problem Fludrocortisone may be helpful Other effects include sweating , palpitation, HTN Cardiac effects In the usual therapeutics doses: tachycardia, flattened T wave, prolonged QT interval, and depr essed ST segment Because the drug prolong conduction time, their use in patients with preexisting conduction defects is contraindicated. The drug should be discontinued several days before elective surgery because of occurrence of hypertensive episodes during surgery in patients receiving TCAs. Neurlogical effects Desipramine and protriptyline are associated with psychomotor stimulation: Myoclonic jerks and tremors of tongue and upper extremities Speech block Paresthesia Peroneal palsy Ataxia Amoxapine is unique in causing Parkinsonian symptoms Akathisia Dyskinesia rarely; neuroleptic malignant syndrome Maprotiline may cause seizures if Dose increase too quickly Dose keep at high level for too long Overall TCAs have relatively low risk for inducing seizures, except in patients who are at risk for seizures. Allergic and hematological effects Rash in 4-5 % in maprotiline Jaundice is rare Agranulocytosis, leukopenia and leukocytosis are rare. However , a patient with fever or sore throat during the first few months of TCA treatment, should have a CBC immediately. Other adverse effects : Weight gain Impotence Gynecomastia Amenorrhea Nausea Hepatitis Vomiting SIADH SSRI Major differences between them is different pharmacokinetics profiles Fluoxetine has the longest half life of 2-3 days, others of about 2o hrs. All well absorbed orally and metabolized in the liver Paroxetine and fluoxetine are metabolized by CYP 2D6, be careful in coadministration of drugs with the same enzyme metabolizer Fluvoxamine inhibits the CYP 3A4, so interfere with terfenadine and astemizole. If taken with food, it reduce nausea and diarrhea. Therapeutic indications of SSRI Depression ; they are first line in the general population ( mild and moderate Dep. ), the elderly, the medically ill and those who are pregnant. Serteraline may be more effective for treatment of severe depression with melancholia Over 50% of persons who respond poorly to one SSRI will respond favorably to another. Augmentation strategies In depressed persons with partial response : Bupropion Lithium Levothyroxine Sympathomimetics Pindolol Clonazepam Suicide Markedly reduce the risk of suicide Depression during pregnancy No documented adverse reaction SSRI may produce a self limited neonatal withdrawal syndrome that consist of jitterness and mild tachypnea, it begins several hrs after birth and may persist for days to a few weeks. It is rare and does not interfere with feeding. Postpartum depression(+/- psychotic feature) Depression in the Elderly and Medically ill Precise diagnostic evaluation to rule out dementia and delirium. They are less well tolerated by persons with preexisting GI symptoms. Chronic depression They have to continue taking SSRI`s for at least 1 year. Depression in children Children of depressed adults are at increased risk of depression. Adverse effects in children includes GI symptoms, insomnia, motor restlessness, social disinhibition, and hypomania or mania; so SSRI use with small doses. OCD Fluvoxamine and Serteraline are approved for treatment of pediatric OCD Effective dose for OCD is higher than those required for depression. Panic Disorders SSRI`s are far superior to benzodiazepines for treatment of panic disorder with depression. Are effective for childhood panic symptoms Social Phobia Posttraumatic Stress Disorder SSRI`s are more effective than TCAD and MAO`s inhibitor Marked improvement of both intrusive and avoidant symptoms. Specific phobias, GAD, separation anxiety Bulimia Nervosa and other Eating Disorder Fluoxetine Obesity ; fluoxetine in combination with behavioral program Premenstural Dysphoric Disorder Fluoxetine and Serteraline Adverse Reactions of SSRI`s Sexual dysfunction: inhibited orgasm and decreased libido. Gastrointestinal : nausea, diarrhea, vomiting, dyspepsia, anorexia. Weight Gain Headaches; 18-20 % Anxiety Insomnia and Sedation Vivid dreams and Nightmares Seizures Extrapyramidal Symptoms Galactorrhea Hypoglycemia , rarely hyponatremia and SIADH Serotonin Syndrome Concurrent administration of an SSRI with MAOI, l- tryptophan, or lithium can rise plasma serotonin concentration Diarrhea Restlessness Agitation , hyperreflexia, autonomic instability, rapid fluctuations of vital signs Myoclonus , seizures, hyperthermia, rigidity, Delirium , coma, cardiovascular collapse and death. SSRI`s Withdrawal Dizziness Weakness Nausea Headaches Rebound depression Anxiety Insomnia Poor concentration Upper respiratory symptoms Paresthesia Migranelike symptoms BUPROPION More effective against symptoms of depression than those of anxiety. Half life 12 hrs. Blockade of dopamine reuptake Therapeutic indications: Depression Bipolar Disorders ADHD Cocaine Detoxification Smoking cesation BUPROPION Adverse reaction Headache Insomnia Upper respiratory symptoms Nausea Restlessness Agitation Irritability Weight loss 25% Dry mouth constipation Trazodone Half life is 6-11 hrs Specific inhibitor of serotonin reuptake Depressive Disorder Insomnia Venlafaxine May have faster onset of action than other antidepressant Most effective drugs for treatment of severe depression with melancholic features & GAD Half life 3.5 hrs( SR-form 9 hrs ) Inhibitor of serotonin & norepinephrine reuptake and weak inhibitor of dopamine reuptake Therapeutic indications Depression GAD OCD Panic Agarophobia , social phobia, ADHD Adverse reactions: Nausea Somnolence Dry mouth Dizziness Constipation Asthenia Anxiety Anorexia Blurred vision Abnormal ejaculation and orgasm Errectile disturbance and impotence Duloxetine Inhibitor of serotonin and norepinephrine MAIO Drugs Used less frequently than others Increase biogenic amine neurotransmitter level There are two type of MAO : A & B MAOA metabolize NEP, SER, EPI MAOB metabolize DOP, TYR Therapeutic indications: Depression, Atypical depression Panic Agarophobia PTSD Eating Disorder Social phobia Pain Disorder
