Transcript Anti depressant Drugs - Isfahan University of Medical Sciences

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 