Selective serotonin reuptake inhibitors drug interactions

Mitchell PB. Drug interactions of clinical significance with selective serotonin reuptake inhibitors. Drug Saf 1997 17 390 106. 

The answer is d. (Kai ung, p 505.) Fluoxetine is a highly selective serotonin re uptake inhibitor (55RI) acting on the 5-1 IT transporter. It forms an active metabolite that is effective for several days. Selective serotonin reuptake inhibitors are inhibitors of cytochrome P450 isoenzymes, which is the basis of potential drug-drug interactions... 

Psychiatric medicines exert multiple effects for two principal reasons. First, they usually interact with more than one receptor type. There are two ways to look at this. You will often hear a medication with multiple receptor interactions called a dirty drug. This is because the more receptor interactions it has, the more effects, and hence side effects, it produces. As a result, great effort has been made to develop newer medications with fewer receptor interactions and, thus, fewer side effects. This effort has been quite successful with antidepressants, as we have moved from the effective but side effect-laden tricyclic antidepressants to newer antidepressants such as selective serotonin reuptake inhibitors. 

Ramamoorthy S, Leibach FH, Mahesh VB, Ganapathy V (1993) Partial purification and characterization of the human placental serotonin transporter. Placenta 14 449-461 Rasmussen BB, Brosen K (2000) Is therapeutic drug monitoring a case for optimizing clinical outcome and avoiding interactions of the selective serotonin reuptake inhibitors Ther DrugMonit 22 143-154... 

A growing number of drugs are used that affect the many neurotransmitters in the brain benzodiazepines and others act on GABAergic transmission antidepressants, such as monoamine oxidase inhibitors and tricyclic antidepressants, are thought to increase the concentration of transmitter amines in the brain and so elevate mood—these will also act at peripheral nerve terminals, so interactions with them are a combination of peripheral and central actions. Levodopa (L-dopa) increases central as well as peripheral dopamine, and the newer class of psychoactive drugs, the selective serotonin reuptake inhibitors (SSRIs) of which the ubiquitous fluoxetine (Prozac) is best known, act in a similar way on serotonergic pathways. 

Monoamine oxidase inhibitors (eg, tranylcypromine, phenelzine) are older antidepressants that are occasionally used for resistant depression. They can cause severe hypertensive reactions when interacting foods or drugs are taken (see Chapters 9 and 30), and they can interact with the selective serotonin reuptake inhibitors (SSRIs). 

Ereshefsky L, Riesenman C, Lam YWF. Serotonin selective reuptake inhibitor drug-interactions and the cytocbrome-P450 system. J Clin Psychiatry 1996 57 17-25. 

Lane RM. Pharmacokinetic drug-interaction potential of selective serotonin reuptake inhibitors. Int Clin Psychopharmacol 1996 11 31-61. 

Sproule BA, Naranjo CA, Bremner KE, et al. Selective serotonin reuptake inhibitors and CNS drug interactions-a critical review of the evidence. Clin Pharmacokinet 1997 33 454-471. 

Baker GB, Fang J, Sinha S, et al. Metabolic drug interactions with selective serotonin reuptake inhibitor (SSRI) antidepressants. Neurosci Biobehav Rev 1998 22 325-333. 

Hemeryck A, Belpaire FM. Selective serotonin reuptake inhibitors and cytochrome P-450 mediated drug-drug interactions an update. Curr Drug Metab 2002 3 13-37. 

Selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine, interact with drugs including clarithromycin, warfarin, phenelzine, benzotropine, chlorpromazine, diazepam, and cyproheptadine. Cigarette smokers metabolize SSRIs faster. 

Aspirin produces an antipyretic and anti-inflammatory effect primarily by irreversibly inhibiting cyclooxygenase (thus having similar effects to NSAIDs). It possesses an antiplatelet effect that may have additive effect with other drugs with a similar effect (e.g, selective serotonin reuptake inhibitors) and those which affect other aspects of blood clotting. The risk of interactions and adverse effects are reduced by using a lower dose (e.g. 75 mg) fortunately, a full antiplatelet effect is seen at this dose. This is considered in Part 1, Cardiovascular Drugs. 

Several studies have examined the interaction between selective serotonin reuptake inhibitors (SSRIs) and P-gp and have shown that not all members of this class of drugs are P-gp substrates. Concentrations of paroxetine and venlafaxine/ but not fluoxetine/ were significantly increased in the brains of mdrla/b (—j—) knockout mice compared to concentrations in the wild-type mice.(100) In cell culture studies/ sertraline/ its metabolite desmethylsertraline/ and paroxetine were shown to be potent inhibitors of P-gp however/ citalopram and venlafaxine were only weak inhibitors (101/ 102). 

MAOI and SSRI are acronyms for two types of antidepression medication. MAOI stands for monoamine oxidase inhibitor. MAOIs must be prescribed and used with caution because they tend to dangerously interact with other types of drugs.Today, other forms of antidepressants are usually prescribed for depression patients first. If those medicines do not work, MAOIs are sometimes used with caution. People taking MAOIs have to restrict their diets and watch what other drugs and medicines they take in order to prevent interactions. SSRI, an antidepressant that is more commonly used, stands for selective serotonin reuptake inhibitor.They are generally able to be tolerated by more people and can be used for more minor depressive illnesses. 

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