What are the next steps for a patient with depression, anxiety, and post-traumatic stress disorder (PTSD) who is currently taking mirtazapine (Remeron) 45mg and desvenlafaxine (Pristiq) 100mg/day, but is now experiencing worsening symptoms with fatigue and lack of motivation?

From the Guidelines

I strongly recommend discussing with your healthcare provider about adjusting your medication regimen since your symptoms are worsening despite being on mirtazapine 45mg and desvenlafaxine 100mg daily, as the most recent and highest quality study suggests that treatment adjustments should be made after 8 weeks if symptoms persist or worsen 1. Your provider might consider increasing the desvenlafaxine dose (up to 200mg daily), switching one medication, or adding an adjunctive treatment like bupropion (Wellbutrin) which can help specifically with fatigue and motivation issues. In the meantime, incorporate regular physical activity (even just 20-30 minutes of walking daily), maintain a consistent sleep schedule, practice stress reduction techniques like deep breathing or mindfulness meditation, and consider psychotherapy alongside medication. Your worsening symptoms may indicate that your current medication combination needs adjustment, as neurotransmitter responses can change over time. Sometimes the body develops tolerance to antidepressants, requiring dose adjustments or medication changes. The combination of mirtazapine (which affects serotonin, norepinephrine, and histamine) and desvenlafaxine (an SNRI) should theoretically provide good coverage for depression, anxiety, and PTSD symptoms, but individual responses vary significantly, and medication effectiveness can change over time. Given that you have symptoms of both depression and anxiety, prioritizing treatment of depressive symptoms or using a unified protocol that combines cognitive behavior therapy (CBT) treatments for depression and anxiety may be beneficial, as suggested by recent guidelines 1. Key considerations for treatment adjustments include:

• Assessing follow-through and compliance with treatment recommendations
• Evaluating patient satisfaction with treatment and symptom relief
• Identifying and addressing obstacles to compliance
• Considering alternative interventions or adjustments to the treatment regimen if symptoms persist or worsen despite good adherence.

From the FDA Drug Label

Monitor all antidepressant-treated patients for any indication of clinical worsening and emergence of suicidal thoughts and behaviors, especially during the initial few months of drug therapy, and at times of dosage changes. Counsel family members or caregivers of patients to monitor for changes in behavior and to alert the healthcare provider Consider changing the therapeutic regimen, including possibly discontinuing mirtazapine tablets, in patients whose depression is persistently worse, or who are experiencing emergent suicidal thoughts or behaviors.

The patient's symptoms of depression, anxiety, and PTSD are worsening, with increased fatigue and lack of motivation, while currently taking mirtazapine 45mg and desvenlafaxine 100mg/day.

• Clinical Worsening: The patient's condition is worsening, which may indicate the need for a change in the therapeutic regimen.
• Treatment Options: Consider changing the dosage or discontinuing mirtazapine tablets, as the patient's depression is persistently worse 2. It is recommended to consult with a healthcare provider to determine the best course of action for the patient's specific situation.

From the Research

Current Treatment and Symptoms

• The user is currently taking mirtazapine 45mg and desvenlafaxine 100mg/day, which was initially helping but is now associated with worsening symptoms, including fatigue and lack of motivation.
• The combination of mirtazapine and desvenlafaxine is not directly addressed in the provided studies, but the efficacy of each medication individually and in combination with other agents is discussed.

Alternative Treatment Options

• Quetiapine has been studied as an adjunct to selective serotonin reuptake inhibitors (SSRIs) or venlafaxine in patients with major depression, comorbid anxiety, and residual depressive symptoms 3.
• The addition of quetiapine to SSRI/venlafaxine therapy has been shown to be effective in reducing depressive and anxiety symptoms, with a rapid onset of action 3.
• Combined treatment with venlafaxine and quetiapine has also been studied in treatment-resistant depression, showing good efficacy and safety 4.

Mirtazapine Efficacy

• Mirtazapine has been compared to other antidepressants, including SSRIs and venlafaxine, in the treatment of major depression 5.
• Mirtazapine was found to be more effective than SSRIs and venlafaxine in some studies, with a faster onset of action and a unique adverse event profile 5.

PTSD Treatment

• Quetiapine has been studied in the treatment of post-traumatic stress disorder (PTSD), with preliminary findings supporting its efficacy in ameliorating symptoms 6.
• First-line treatment of PTSD typically involves psychotherapy, with pharmacotherapy used for residual symptoms or in conjunction with psychotherapy 7.
• Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), such as venlafaxine, are commonly used in the treatment of PTSD 7.