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Chapter: Clinical Pharmacology: Psychotropic drugs

Selective serotonin reuptake inhibitors

Developed to treat depression with fewer adverse reactions.

Selective serotonin reuptake inhibitors


Developed to treat depression with fewer adverse reactions,


SSRIs,are chemically different from MAOIs and TCAs. (See Putting a new stress on SSRIs.)


Some of the SSRIs currently available are:


·                 citalopram


·                 duloxetine


·                 escitalopram


·                 fluoxetine


·                 fluvoxamine


·                 paroxetine


·                 sertraline


·                 venlafaxine. (See Stopping SSRIs.)



SSRIs are absorbed almost completely after oral administration and are highly protein-bound.

Metabolism and excretion

SSRIs are primarily metabolized in the liver and are excreted in urine.



SSRIs inhibit the neuronal reuptake of the neurotransmitter sero-tonin.



SSRIs are used to treat the same major depressive episodes as TCAs and have the same degree of effectiveness. Fluvoxamine, fluoxetine, sertraline, and paroxetine are also used to treat obses-sive-compulsive disorder. Fluoxetine has also been approved for the treatment of bulimia. Paroxetine is also indicated for social anxiety disorder.


Venlafaxine is an antidepressant drug that’s chemically differ-ent from other antidepressants and has unique properties in terms of absorption and mechanism of action. It has been particularly ef-fective in patients with very severe depression.


Don’t panic, but there’s more…


SSRIs may also be useful in treating panic disorders, eating disor-ders, personality disorders, impulse control disorders, and anxiety disorders. Several SSRIs are approved for premenstrual (dysphor-ic) disorder.

Drug interactions

Drug interactions associated with SSRIs involve their ability to competitively inhibit a liver enzyme that’s responsible for oxida-tion of numerous drugs, including TCAs, carbamazepine, metoprolol, flecainide, encainide, and antipsychotics, such as clozapine and thioridazine.


They don’t mix with MAOIs


The use of SSRIs with MAOIs can cause serious, potentially fatal reactions. Individual SSRIs also have their own particular interac-tions. (See Adverse reactions to SSRIs.)


§    Use of citalopram and paroxetine with warfarin may lead to in-creased bleeding.


§    Carbamazepine may increase clearance of citalopram.


§    Fluoxetine increases the half-life of diazepam and displaces highly protein-bound drugs, leading to toxicity.


§    Fluvoxamine use with diltiazem hydrochloride may cause bradycardia.


§    Paroxetine shouldn’t be used with tryptophan because this com-bination can cause headache, nausea, sweating, and dizziness.


§    Paroxetine may increase procyclidine levels, causing increased anticholinergic effects.


§    Cimetidine, phenobarbital, and phenytoin may reduce paroxe-tine metabolism by the liver, increasing the risk of toxicity.


§    Paroxetine and sertraline may interact with other highly pro-tein-bound drugs, causing adverse reactions to either drug. (See Risks of antidepressants.)

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