Since vilazodone is primarily a substrate of CYP3A4, strong CYP3A4 inhibitors such as ketoconazole can increase the serum concentration of vilazodone by 50% or more. On the other hand, vilazodone is neither a potent inhibitor nor a strong inducer of any CYP isoenzymes. It may be a mild inducer of CYP2C19.
E. Monoamine Oxidase Inhibitors
MAOIs are associated with two classes of serious drug interactions. The first of these is the pharmacodynamic interaction of MAOIs with serotonergic agents including SSRIs, SNRIs, and most TCAs along with some analgesic agents such as meperidine. These combinations of an MAOI with a serotonergic agent may result in a life-threatening serotonin syndrome (see Chapter 16). The serotonin syndrome is thought to be caused by over-stimulation of 5-HT receptors in the central gray nuclei and the medulla. Symptoms range from mild to lethal and include a triad of cognitive (delirium, coma), autonomic (hypertension, tachycardia, diaphoreses), and somatic (myoclonus, hyperreflexia, tremor) effects. Most serotonergic antidepressants should be discontinued at least 2 weeks before starting an MAOI. Fluoxetine, because of its long half-life, should be discontinued for 4–5 weeks before an MAOI is initiated. Conversely, an MAOI must be discontinued for at least 2 weeks before starting a serotonergic agent.
The second serious interaction with MAOIs occurs when an MAOI is combined with tyramine in the diet or with sympathomimetic substrates of MAO. An MAOI prevents the breakdown of tyramine in the gut, and this results in high serum levels that enhance peripheral noradrenergic effects, including raising blood pressure dramatically. Patients on an MAOI who ingest large amounts of dietary tyramine may experience malignant hypertension and subsequently a stroke or myocardial infarction. Thus, patients taking MAOIs require a low-tyramine diet and should avoid foods such as aged cheeses, tap beer, soy products, and dried sausages, which contain high amounts of tyramine (see Chapter 9). Similar sympathomimetics also may cause significant hypertension when combined with MAOIs. Thus, over-the-counter cold preparations that contain pseudoephedrine and phenylpropanolamine are contraindicated in patients taking MAOIs.
• Fluvoxamine: Similar to above but approved only for obsessive-compulsive behavior • Duloxetine• Venlafaxine• LevomilnacipranModerately selective blockade of NET and SERT Acute increase in serotonergic and adrenergic synapticactivity•otherwiselike SSRIs Major depression, chronic paindisorders•fibromyalgia,perimenopausal symptoms Toxicity: Anticholinergic, sedation, hypertension(venlafaxine)•Interactions: Some CYP2D6 inhibition (duloxetine, desvenlafaxine)•CYP3A4interactionswith levomilnacipran • Desvenlafaxine:
Desmethyl metabolite of venlafaxine, metabolism is by phase II rather than CYP phase I • Milnacipran:
Approved only for fibromyalgia in the USA; significantly more selective for NET than SERT; little effect on DAT
TETRACYCLICS, UNICYCLIC
Citalopram Generic, Celexa
Escitalopram Generic, Lexapro
Fluoxetine Generic, Prozac, Prozac Weekly
Paroxetine Generic, Paxil
Duloxetine Generic, Cymbalta
Venlafaxine Generic, Effexor
Trazodone Generic, Desyrel
Amitriptyline Generic, Elavil