What antidepressants should be avoided in patients with anxiety disorder?

From the Guidelines

When treating anxiety, it's crucial to avoid certain antidepressants that may worsen anxiety symptoms, particularly paroxetine, due to its association with increased risk of suicidal thinking or behavior and discontinuation syndrome, as noted in the clinical practice guideline for the assessment and treatment of children and adolescents with anxiety disorders 1.

Key Considerations for Antidepressant Selection in Anxiety

• The choice of antidepressant should be guided by the potential for drug-drug interactions, with fluvoxamine having a greater potential for such interactions due to its effect on multiple CYP enzymes 1.
• Citalopram should be avoided in patients with long QT syndrome due to the risk of QT prolongation associated with Torsade de Pointes, ventricular tachycardia, and sudden death at daily doses exceeding 40 mg/d 1.
• A conservative approach to initiating antidepressant therapy, starting with a subtherapeutic dose as a "test" dose, can help mitigate initial adverse effects such as anxiety or agitation 1.
• Systematic assessment of treatment response using standardized symptom rating scales is recommended to optimize the benefit-to-harm ratio and achieve remission 1.

Recommendations for Safe Prescribing Practices

• Medical education, training, and experience are necessary to safely and effectively prescribe antidepressant medications, especially in the context of anxiety disorders 1.
• Parental oversight of medication regimens is of paramount importance in children and adolescents 1.
• Clinicians should be cautious when starting the second non-MAOI serotonergic drug, initiating at a low dose, increasing the dose slowly, and monitoring for symptoms, especially in the first 24 to 48 hours after dosage changes 1.

From the FDA Drug Label

Patients should be cautioned about the risk of serotonin syndrome with the concomitant use of Prozac and triptans, tramadol or other serotonergic agents. CNS active drugs — The risk of using Prozac in combination with other CNS active drugs has not been systematically evaluated. Nonetheless, caution is advised if the concomitant administration of Prozac and such drugs is required Antipsychotics — Some clinical data suggests a possible pharmacodynamic and/or pharmacokinetic interaction between SSRIs and antipsychotics Concomitant use of Prozac and pimozide is contraindicated (see CONTRAINDICATIONS). Benzodiazepines — The half–life of concurrently administered diazepam may be prolonged in some patients

The antidepressants to avoid in those with anxiety are not explicitly stated. However, based on the information provided, caution is advised when using fluoxetine with other CNS active drugs, antipsychotics, or benzodiazepines.

• Pimozide is contraindicated with fluoxetine.
• Thioridazine should not be administered with fluoxetine or within a minimum of 5 weeks after fluoxetine has been discontinued. It is essential to monitor clinical status and consider lower initial doses and conservative titration schedules when combining fluoxetine with other medications 2.

From the Research

Antidepressants to Avoid in Those with Anxiety

• Benzodiazepines should be avoided or used only short term in patients with anxiety, particularly post-traumatic stress disorder (PTSD), due to potential depressogenic effects and the possibility that they may promote or worsen PTSD 3
• Monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs) have significant adverse effects, such as cardiovascular complications, and safety issues, such as ease of overdose, making them less desirable options for patients with anxiety 3
• Bupropion, a predominantly noradrenergic reuptake inhibitor, was found to be ineffective in PTSD in an open-label study, suggesting it may not be a suitable option for patients with anxiety 3

Alternative Treatment Options

• Selective serotonin reuptake inhibitors (SSRIs) are considered a first-line treatment for anxiety disorders, including generalized anxiety disorder (GAD), panic disorder, and social anxiety disorder, due to their efficacy and relatively favorable adverse effect profile 3, 4, 5, 6
• Serotonin-potentiating non-SSRIs, such as venlafaxine, nefazodone, trazodone, and mirtazapine, may be considered as second-line treatment options for patients with anxiety who do not respond to SSRIs or have intolerable side effects 3
• Buspirone, a non-benzodiazepine anxiolytic, may be effective in treating anxiety disorders, particularly GAD, although the evidence is primarily based on open-label studies 3, 6