Remarks y SSRIs for panic disorder examined included: citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine and sertraline. Individual analyses indicated sertraline and escitalopram may be the most efficacious with lowest risk of adverse effects. Fluvoxamine, paroxetine and fluoxetine indicated favourable efficacy but higher risk of adverse events. Citalopram indicated minimal efficacy and high risk of adverse events. However, individual analyses are based on limited data and should be interpreted with caution. y TCAs for panic disorder examined included imipramine and clomipramine. y SSRIs for GAD examined included citalopram, escitalopram, fluoxetine, paroxetine and sertraline. Paroxetine was the only SSRI that demonstrated increased risk of adverse events (dropout) relative to placebo. y Evidence on the use of TCAs (imipramine) for GAD was limited and indicated they did not demonstrate a significant effect relative to placebo. y TCAs are generally less well tolerated than SSRIs and therefore are recommended for consideration in cases where SSRIs are not available for adults with panic disorder. y Antidepressants should only be offered in those contexts where health workers are competent (e.g. qualified, trained and supervised) to prescribe psychotropic medicines. y Psychological interventions should be offered only in contexts where individuals are competent (e.g. qualified, trained and supervised) to provide them and demonstrate necessary competencies to do so. y In resource-constrained settings, antidepressants (SSRIs for GAD; SSRIs as first-line treatment and then TCAs as second-line treatment for panic disorder) that are accessible should be favoured, as evidence does not indicate a statistically significant difference between the individual antidepressant medicines in these classes for anxiety disorders. y TCAs are generally less well tolerated than SSRIs and also generally considered less safe, due to anticholinergic side-effects, toxicity, psychomotor and cognitive impairment risks, and lethality risks in cases of acute intoxication or overdose. TCAs are therefore recommended for consideration in cases where SSRIs are not available for adults with panic disorder. y TCAs should be avoided in older adults and in people diagnosed with glaucoma, heart conditions, prostatism or other prostate conditions, or at risk of these conditions. y Consider increased risk of bleeding associated with SSRIs, particularly for older people or people taking other medicines that can damage the gastrointestinal mucosa or interfere with clotting (e.g. non-steroidal anti-inflammatory drugs [NSAIDs]). y Antidepressants should be offered combined with psychological treatments, when sufficient resources are available.

Implementation considerations y Providers should keep in mind the possible adverse effects associated with antidepressant medicines, treatment availability and individual preferences. Discontinuities in drug availability (common in LMICs) may interfere with continuation of treatment. y Specific types of antidepressants selected should carefully consider factors such as demographic characteristics (e.g. higher risks and side-effects that may be associated with pregnancy or older age), side-effects profiles (e.g. sexual dysfunction, sleep problems, weight gain) and availability (e.g. continuous availability, costs). y Support the person in making a decision between antidepressants and psychological interventions (if available), based on providing relevant information (e.g. possible side-effects, costs). Before prescribing medicines, discuss treatment options and any concerns the person has about taking medicines. y Explain rationale for prescribing and provide written and verbal information on benefits and harms, side-effects, drug interactions, the importance of taking medicines as prescribed and the likely time to improvement in symptoms. y Regularly review the effectiveness of the medicine and side-effects with the person during the first three months of treatment and every three months afterwards. For adults who experience side-effects after starting medicine, consider closer monitoring of their symptoms, reducing the dose of the medicine or stopping the medicine gradually and offering alternative interventions. y For adults under 30 years of age who are prescribed antidepressants:

• Inform them of increased risk of suicidal thinking and self-harm behaviour among younger people when taking these medicines.
• Ensure follow-up within one week after initiating the medicines if at all possible.
• Monitor and follow-up on suicidal thinking and self-harm on regular (e.g. weekly) basis within the first month after initiating the medicine or changing the dose. y If the medicine is effective, continue use for at least six months after remission to reduce likelihood of relapse.