What alternative medications can be used to treat anxiety and depression in a patient who cannot take Selective Serotonin Reuptake Inhibitors (SSRIs)?

From the Guidelines

For individuals who cannot take SSRIs but need medication for anxiety and depression, venlafaxine, a serotonin-norepinephrine reuptake inhibitor (SNRI), is suggested as a first-line alternative 1. When considering alternatives to SSRIs, several factors come into play, including the specific symptoms of anxiety and depression, medical history, and potential side effects.

• SNRIs like venlafaxine (Effexor) or duloxetine (Cymbalta) are often considered first-line alternatives, typically starting at low doses (37.5mg or 30mg respectively) and gradually increasing as needed 1.
• Bupropion (Wellbutrin) is particularly helpful for depression with fatigue or low motivation, usually starting at 150mg daily.
• Mirtazapine (Remeron) can be beneficial for those with sleep disturbances or appetite issues, typically prescribed at 15-30mg at bedtime.
• For anxiety symptoms, buspirone (BuSpar) at 5-10mg twice daily can be effective without SSRI-related side effects. These medications work through different mechanisms than SSRIs - SNRIs affect both serotonin and norepinephrine, bupropion primarily affects dopamine and norepinephrine, while mirtazapine has a unique profile affecting multiple neurotransmitter systems. It's essential to consult with a healthcare provider to determine the most appropriate medication and dosage, considering the individual's specific needs and health status 1.

From the FDA Drug Label

Bupropion inhibits the reuptake of dopamine and norepinephrine. Bupropion and its metabolites (erythrohydrobupropion, threohydrobupropion, hydroxybupropion) are CYP2D6 inhibitors Therefore, coadministration of bupropion hydrochloride extended-release tablets (XL) with drugs that are metabolized by CYP2D6 can increase the exposures of drugs that are substrates of CYP2D6. Such drugs include certain antidepressants (e.g., venlafaxine, nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, and sertraline)

Bupropion can be used as an alternative to SSRIs for treating anxiety and depression.

• It works by inhibiting the reuptake of dopamine and norepinephrine.
• However, it is a CYP2D6 inhibitor, which may interact with other drugs that are metabolized by CYP2D6, such as certain antidepressants.
• The dose of these drugs may need to be adjusted when coadministered with bupropion.
• It is essential to use caution when administering bupropion with other drugs that lower the seizure threshold or have dopamine agonist effects.
• The consumption of alcohol during treatment with bupropion should be minimized or avoided.
• Concomitant use of MAOIs and bupropion is contraindicated due to the increased risk of hypertensive reactions 2.

From the Research

Alternatives to SSRIs for Anxiety and Depression

If an individual cannot take SSRIs, there are alternative medications that can be considered for anxiety and depression. These include:

• Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs) such as venlafaxine, duloxetine, and milnacipran 3, 4
• Atypical antidepressants like mirtazapine 5
• Tetracyclic antidepressants (TeCAs) such as amoxapine and maprotiline 6

SNRIs as an Alternative

SNRIs work by inhibiting the reuptake of both serotonin and norepinephrine, which can help alleviate symptoms of anxiety and depression. Some key points about SNRIs include:

• Venlafaxine has an ascending dose-response curve, with greater efficacy at higher doses 3
• Duloxetine has a more balanced profile of binding to serotonin and norepinephrine transporters 3
• Milnacipran has few pharmacokinetic and pharmacodynamic interactions with other drugs 3

Efficacy and Tolerability of SNRIs

Studies have shown that SNRIs can be effective in treating anxiety and depression, with some advantages over SSRIs. For example:

• Venlafaxine has been shown to be effective in treating generalized anxiety disorder, social anxiety disorder, and panic disorder 3
• Duloxetine has been shown to be effective in treating major depressive disorder, as well as diabetic peripheral neuropathic pain, fibromyalgia, and musculoskeletal pain 3
• SNRIs may have a more favorable tolerability profile compared to SSRIs, with fewer sexual side effects and less risk of serotonin syndrome 4

Considerations for Treatment

When considering treatment with SNRIs, it's essential to weigh the potential benefits and risks. Some key considerations include:

• Dose-dependent blood pressure elevation with venlafaxine 3
• Potential for drug-drug interactions with duloxetine due to its inhibition of CYP2D6 3
• Importance of monitoring blood pressure and pulse with SNRIs, particularly at higher doses 3, 4