Can a patient combine MAOI with SSIRs or TCA?

1.

Elsevier ClinicalKey Drug Monograph

Content last updated: March 4, 2024.

Interactions Selective serotonin reuptake inhibitors: (Contraindicated) Due to the risk of serotonin syndrome, monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders are contraindicated for use with selective serotonin reuptake inhibitors (SSRIs). MAOIs should not be used within 5 weeks of discontinuing treatment with fluoxetine or within 14 days of discontinuing treatment with other SSRIs. Conversely, SSRIs should not be initiated within 14 days of stopping an MAOI. Monitor the patient for serotonin-related effects during therapy transitions.

Interactions Zoloft Solution: (Contraindicated) Due to the risk of serotonin syndrome, monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders are contraindicated for use with selective serotonin reuptake inhibitors (SSRIs). MAOIs should not be used within 5 weeks of discontinuing treatment with fluoxetine or within 14 days of discontinuing treatment with other SSRIs. Conversely, SSRIs should not be initiated within 14 days of stopping an MAOI. Monitor the patient for serotonin-related effects during therapy transitions.

2.

Elsevier ClinicalKey Drug Monograph

Content last updated: May 3, 2024.

Interactions Monoamine oxidase inhibitors: (Contraindicated) Due to the risk of serotonin syndrome, monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders are contraindicated for use with selective serotonin reuptake inhibitors (SSRIs). MAOIs should not be used within 5 weeks of discontinuing treatment with fluoxetine or within 14 days of discontinuing treatment with other SSRIs. Conversely, SSRIs should not be initiated within 14 days of stopping an MAOI. Monitor the patient for serotonin-related effects during therapy transitions.

3.

Elsevier ClinicalKey Drug Monograph

Content last updated: May 4, 2024.

Interactions Monoamine oxidase inhibitors: (Contraindicated) Due to the risk of serotonin syndrome, monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders are contraindicated for use with selective serotonin reuptake inhibitors (SSRIs). MAOIs should not be used within 5 weeks of discontinuing treatment with fluoxetine or within 14 days of discontinuing treatment with other SSRIs. Conversely, SSRIs should not be initiated within 14 days of stopping an MAOI. Monitor the patient for serotonin-related effects during therapy transitions.

4.

Elsevier ClinicalKey Drug Monograph

Content last updated: March 4, 2024.

Interactions Tranylcypromine: (Contraindicated) Due to the risk of serotonin syndrome, monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders are contraindicated for use with selective serotonin reuptake inhibitors (SSRIs). MAOIs should not be used within 5 weeks of discontinuing treatment with prozac or within 14 days of discontinuing treatment with other SSRIs. Conversely, SSRIs should not be initiated within 14 days of stopping an MAOI. Monitor the patient for serotonin-related effects during therapy transitions.

5.

Elsevier ClinicalKey Derived Clinical Overview

The combined use of SSRIs and MAOIs is contraindicated. • Despite serotonin syndrome being relatively rare, it is worth consideration in a differential even if common supporting elements to the diagnosis are absent such as meeting Hunter criteria, MAOI involvement, rapid onset, and hyperthermia. • Studies have suggested that genetic polymorphisms at the sites of CYP2D6 and T102C may contribute to individuals developing serotonin syndrome.

6.

Food and Drug Administration (DailyMed).

Publish date: November 2, 2022.

Drug Interactions 7 DRUG INTERACTIONS Table 9 presents clinically significant drug interactions with paroxetine. Table 9: Clinically Significant Drug Interactions with Paroxetine Monoamine Oxidase Inhibitors (MAOIs) Clinical Impact The concomitant use of SSRIs, including paroxetine, and MAOIs increases the risk of serotonin syndrome. Intervention Paroxetine is contraindicated in patients taking MAOIs, including MAOIs such as linezolid or intravenous methylene blue [see Dosage and Administration ( 2.5 ), Contraindications ( 4 ), Warnings and Precautions ( 5.2 )] . Examples selegiline, tranylcypromine, isocarboxazid, phenelzine, linezolid, methylene blue Pimozide and Thioridazine Clinical Impact Increased plasma concentrations of pimozide and thioridazine, drugs with a narrow therapeutic index, may increase the risk of QTc prolongation and ventricular arrhythmias. Intervention Paroxetine is contraindicated in patients taking pimozide or thioridazine [see Contraindications ( 4 )]. Other Serotonergic Drugs Clinical Impact The concomitant use of serotonergic drugs with paroxetine increases the risk of serotonin syndrome. Intervention Monitor patients for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of paroxetine and/or concomitant serotonergic drugs [see Warnings and Precautions ( 5.2 )] . Examples other SSRIs, SNRIs, triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, St. John’s Wort Drugs that Interfere with Hemostasis (antiplatelet agents and anticoagulants) Clinical Impact The concurrent use of an antiplatelet agent or anticoagulant with paroxetine may potentiate the risk of bleeding. Intervention Inform patients of the increased risk of bleeding associated with the concomitant use of paroxetine and antiplatelet agents and anticoagulants.

7.

Food and Drug Administration (DailyMed).

Publish date: June 4, 2023.

Precautions The extent to which SSRI TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary). Concomitant use of tricyclic antidepressants with drugs that can inhibit cytochrome P450 2D6 may require lower doses than usually prescribed for either the tricyclic antidepressant or the other drug. Furthermore, whenever one of these other drugs is withdrawn from co-therapy, an increased dose of tricyclic antidepressant may be required. It is desirable to monitor TCA plasma levels whenever a TCA is going to be co-administered with another drug known to be an inhibitor of P450 2D6. Close supervision and careful adjustment of dosage are required when this drug is given concomitantly with anticholinergic or sympathomimetic drugs. Patients should be warned that while taking this drug their response to alcoholic beverages may be exaggerated. If desipramine hydrochloride is to be combined with other psychotropic agents such as tranquilizers or sedative/hypnotics, careful consideration should be given to the pharmacology of the agents employed since the sedative effects of desipramine hydrochloride and benzodiazepines (e.g., chlordiazepoxide or diazepam) are additive. Both the sedative and anticholinergic effects of the major tranquilizers are also additive to those of desipramine hydrochloride. Concomitant use of Monoamine Oxidase Inhibitors (MAOIs) and serotonergic drugs may potentially cause life threatening adverse events (see CONTRAINDICATIONS , WARNINGS , and DOSAGE AND ADMINISTRATION ).

8.

Food and Drug Administration (DailyMed).

Publish date: March 5, 2024.

Drug Interactions In addition, certain drugs inhibit the activity of the isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary). Concomitant use of tricyclic antidepressants with drugs that can inhibit cytochrome P450 2D6 may require lower doses than usually prescribed for either the tricyclic antidepressant or the other drug. Furthermore, whenever one of these other drugs is withdrawn from co-therapy, an increased dose of tricyclic antidepressant may be required. It is desirable to monitor TCA plasma levels whenever a TCA is going to be co-administered with another drug known to be an inhibitor of P450 2D6. Monoamine Oxidase Inhibitors (MAOIs) (See CONTRAINDICATIONS , WARNINGS , and DOSAGE AND ADMINISTRATION .) Serotonergic Drugs (See CONTRAINDICATIONS , WARNINGS , and DOSAGE AND ADMINISTRATION .)

9.

Walter HJ, Bukstein OG, Abright AR, et al. Journal of the American Academy of Child and Adolescent Psychiatry. 2020;59(10):1107-1124. doi:10.1016/j.jaac.2020.05.005.

Publish date: October 4, 2020.

Serotonin syndrome, caused by elevated brain serotonin levels, can be triggered when serotonergic medications are combined. Symptoms can arise within 24 to 48 hours after combining medications and are characterized by mental status changes (confusion, agitation, anxiety); neuromuscular hyperactivity (tremors, clonus, hyperreflexia, muscle rigidity); and autonomic hyperactivity (hypertension, tachycardia, arrhythmias, tachypnea, diaphoresis, shivering, vomiting, diarrhea). Advanced symptoms include fever, seizures, arrhythmias, and unconsciousness, which can lead to fatalities. Treatment is hospital based and includes discontinuation of all serotonergic agents and supportive care with continuous cardiac monitoring. Monoamine oxidase inhibitors (MAOIs), including phenelzine, isocarboxazid, moclobemide, isoniazid, and linezolid play a role in most cases of serotonin syndrome and should be avoided in combination with any other serotonergic drug, including another MAOI. Moreover, caution should be exercised when combining two or more non-MAOI serotonergic drugs, including antidepressants (eg, SSRIs, SNRIs, TCAs, atypical antidepressants); opioids and other pain medications (eg, tramadol, meperidine, methadone, fentanyl); stimulants (eg, amphetamine and possibly methylphenidate classes); cough/cold/allergy medications (eg, dextromethorphan, chlorpheniramine); other over-the-counter products (eg, St. John’s wort, L-tryptophan, diet pills); and illicit drugs (eg, ecstasy, methamphetamine, cocaine, LSD). Caution entails starting the second non-MAOI serotonergic drug at a low dose, increasing the dose slowly, and monitoring for symptoms, especially in the first 24 to 48 hours after dosage changes. Each SSRI has special prescribing considerations. Paroxetine, fluvoxamine, and sertraline have been associated with discontinuation syndrome (see below for syndrome description).