What are the potential drug-drug interactions between psychotropic medications, such as antipsychotics, antidepressants, and mood stabilizers, and medications prescribed to treat hypertension (High Blood Pressure), diabetes (Diabetes Mellitus), migraines, and hyperlipidemia (High Cholesterol)?

From the Guidelines

Drug-drug interactions between psychotropic medications and those for common medical conditions are a critical concern that requires careful monitoring to prevent adverse effects, particularly in older adults or those with multiple chronic conditions. When considering the management of patients on psychotropic medications such as antipsychotics, antidepressants, and mood stabilizers who are also being treated for hypertension, diabetes, migraines, or high cholesterol, it is essential to be aware of potential drug-drug interactions that could affect morbidity, mortality, and quality of life.

• Antipsychotics like quetiapine and olanzapine can worsen blood glucose control in diabetic patients taking medications such as metformin or insulin, potentially requiring dose adjustments of the diabetes medications, as noted in studies focusing on the management of diabetes in patients with mental health conditions 1.
• Many antidepressants, particularly SSRIs like fluoxetine and paroxetine, can inhibit CYP450 liver enzymes that metabolize beta-blockers and statins, potentially increasing blood levels of these medications and causing side effects, which is a concern when managing patients with hypertension or high cholesterol.
• Mood stabilizers like lithium interact dangerously with diuretics and ACE inhibitors used for hypertension, as these can increase lithium levels and lead to toxicity, highlighting the need for careful monitoring of drug levels and renal function in patients on lithium therapy.
• The risk of serotonin syndrome, a potentially life-threatening condition, is increased when triptans are combined with SSRIs or SNRIs for migraine treatment, necessitating cautious prescribing practices.
• Carbamazepine, a mood stabilizer, can significantly reduce the effectiveness of statins and many other medications through enzyme induction, which has implications for the management of patients with high cholesterol or other conditions requiring these medications. These interactions can occur through various mechanisms, including altered drug metabolism, pharmacodynamic effects where drugs compete for the same receptors, and changes in protein binding that affect drug availability. Given the complexity of these interactions and the potential for adverse outcomes, it is crucial to prioritize regular monitoring of blood pressure, blood glucose, cholesterol levels, and appropriate drug levels when applicable, and to consider deprescribing or adjusting medications when necessary to minimize risk, especially in older adults or those with multiple chronic conditions, as emphasized in guidelines for managing polypharmacy in older patients 1.

From the FDA Drug Label

DRUG INTERACTIONS Diazepam: May potentiate orthostatic hypotension. (7.1,7.2) Alcohol: May potentiate orthostatic hypotension. (7.1) Carbamazepine: Increased clearance of olanzapine. (7.1) Fluvoxamine: May increase olanzapine levels. (7.1) ZYPREXA and Fluoxetine in Combination: Also refer to the Drug Interactions section of the package insert for Symbyax. (7. 1) CNS Acting Drugs: Caution should be used when taken in combination with other centrally acting drugs and alcohol. (7.2) Antihypertensive Agents: Enhanced antihypertensive effect. (7.2) Levodopa and Dopamine Agonists: May antagonize levodopa/dopamine agonists. (7.2) Lorazepam (IM): Increased somnolence with IM olanzapine. (7. 2) Other Concomitant Drug Therapy: When using olanzapine in combination with lithium or valproate, refer to the Drug Interactions sections of the package insert for those products. (7.2)

The drug interactions between psychotropic medications such as antipsychotics (e.g. olanzapine), antidepressants (e.g. fluoxetine), mood stabilizers (e.g. lithium, valproate) and medications prescribed to treat:

• Hypertension: Antihypertensive Agents may have an enhanced antihypertensive effect when used with olanzapine 2.
• Diabetes: No direct information is available.
• Migraines: No direct information is available.
• High cholesterol: No direct information is available. Other interactions include:
• CNS Acting Drugs: Caution should be used when taken in combination with other centrally acting drugs and alcohol 2.
• Levodopa and Dopamine Agonists: May antagonize levodopa/dopamine agonists 2.

From the Research

Drug-Drug Interactions between Psychotropic Medications and Other Medications

• Psychotropic medications, such as antipsychotics, antidepressants, and mood stabilizers, can interact with medications prescribed to treat hypertension, diabetes, migraines, and high cholesterol 3, 4, 5, 6, 7.
• Antipsychotic medications can have a negative metabolic impact, increasing the risk of developing metabolic instability and/or type 2 diabetes, which can interact with medications used to treat diabetes 4.
• Antidepressant medications can influence blood pressure through different effects on adrenergic and serotoninergic pathways, as well as on histaminergic, dopaminergic, and cholinergic systems, which can interact with antihypertensive treatments 7.
• Selective serotonin reuptake inhibitors (SSRIs) are characterized by limited effects on autonomic system activity and a lower impact on blood pressure, making them a safer option for patients with hypertension 7.
• Serotonin-norepinephrine reuptake inhibitors (SNRIs), particularly venlafaxine, carry a greater risk of hypertension, possibly related to greater effects on the sympathetic nervous system, which can interact with medications used to treat hypertension 7.

Interactions with Medications for Hypertension

• Psychotropic medications can increase blood pressure directly or indirectly, via negative metabolic impact and drug/diet interactions, which can interact with antihypertensive agents 3.
• The novel intranasal antidepressant, esketamine, has been shown to increase blood pressure shortly after dosing, but treatment with antihypertensive medications is not typically required 3.
• Tricyclic antidepressants have been associated with increases in blood pressure, as well as orthostatic hypotension, particularly imipramine, which can interact with antihypertensive treatments 7.

Interactions with Medications for Diabetes

• Antipsychotic medications can increase the risk of developing metabolic instability and/or type 2 diabetes, which can interact with medications used to treat diabetes 4.
• Weight gain associated with psychotropic medications can also increase the risk of developing type 2 diabetes, which can interact with medications used to treat diabetes 5.

Interactions with Medications for Migraines and High Cholesterol

• There is limited evidence on the interactions between psychotropic medications and medications used to treat migraines and high cholesterol, but it is possible that certain psychotropic medications can interact with these medications, particularly those that affect blood pressure or metabolism 3, 4, 5, 6, 7.