Generalized anxiety disorder

Chronic excessive worry across multiple domains lasting over 6 months with somatic symptoms. First-line treatment is SSRIs and CBT.

ICD-10 F41.115 drugs

Also known as: GAD

Drugs used for this condition

AEscitalopramFirst line · Selective serotonin reuptake inhibitors (SSRIs)Escitalopram is approved for generalized anxiety disorder. NICE and APA recommend SSRIs as first-line therapy for GAD. Start at 10 mg, may increase to 20 mg. In anxious patients, consider starting at 5 mg for the first week to minimize paradoxical anxiety worsening at treatment initiation. Response develops over 4–8 weeks.
AParoxetineFirst line · Selective serotonin reuptake inhibitor (SSRI)First-line for generalized anxiety disorder. Effect at 4–6 weeks. Dose 20–50 mg daily.
ASertralineFirst line · Selective serotonin reuptake inhibitors (SSRIs)First-line therapy for generalized anxiety disorder in adults alongside escitalopram and venlafaxine. The response is slower than in depression (typically 6–8 weeks). Initial anxiety worsening may occur and should be discussed with the patient. Taper gradually on discontinuation.
BAlprazolamThird line · Benzodiazepines. Short-to-medium-acting anxiolyticsFor GAD, international guidelines (WFSBP 2022, NICE CG113) recommend SSRIs and SNRIs as first-line. Benzodiazepines are considered only briefly for severe symptoms that prevent waiting for SSRI onset. Long-term alprazolam use in GAD is associated with cognitive impairment in older adults, dependence, and a difficult withdrawal syndrome (rebound anxiety, seizure risk), so the dose is tapered gradually rather than stopped abruptly, and courses are kept short.
BBromazepamSecond line · Anxiolytics, benzodiazepine derivativesBromazepam is second-line therapy for generalized anxiety disorder (GAD), used for short-term (up to 2–4 weeks) control of severe anxiety and panic symptoms. The Reinhold 2015 meta-analysis (benzodiazepines in GAD) shows efficacy comparable to other short and intermediate-acting benzodiazepines. NICE CG113, WFSBP, and APA GAD guidelines list SSRIs/SNRIs and CBT as first-line; benzodiazepines are reserved for short-term use in severe anxiety until antidepressant effect develops. Dose 1.5–9 mg/day in 2–3 doses. Continuous treatment should not exceed 8–12 weeks due to dependence risk.
BLorazepamSecond line · Anxiolytics, benzodiazepine derivativesLorazepam is second-line therapy for GAD, used short-term (2–4 weeks) for severe anxiety or panic attacks. Meta-analyses (Mitte 2005, Reinhold 2015) show efficacy comparable to other benzodiazepines. Lorazepam's advantage is absence of active metabolites and glucuronidation metabolism (not CYP) – convenient in older adults, hepatic impairment, and polypharmacy (no significant CYP interactions). NICE CG113 and APA GAD guidelines list SSRIs/SNRIs and CBT as first-line; benzodiazepines short-term only. Dose 1–6 mg/day in 2–3 doses. In older adults, start at 0.5–1 mg/day.
BPregabalinSecond line · Gabapentinoids (antiepileptics)In Europe, pregabalin is EMA-approved for generalized anxiety disorder; not in the US. Per NICE NG113, second-line after SSRI/SNRI failure. Dose 150–600 mg/day. Efficacy comparable to SSRIs with faster onset (1–2 weeks vs 4–6). Advantage: no sexual dysfunction. Disadvantage: dependence/abuse risk, weight gain.
CAgomelatineCase-by-case decision · Antidepressant – melatonin agonist and 5-HT2C antagonistAgomelatine is sometimes used off-label for generalized anxiety disorder; the EMA and AEMPS have approved it only for depression. The supporting evidence is real: a meta-analysis of three placebo-controlled RCTs (Stein et al., 2021) showed reduced anxiety on the Hamilton scale and less functional impairment at 25–50 mg, a 2025 network meta-analysis confirmed the effect, and the drug is listed in the 2023 WFSBP anxiety guidelines. The limitations are substantial: all pivotal trials were manufacturer-sponsored, raising the risk of publication bias; no Spanish or European guideline names agomelatine for anxiety; and first-line treatment remains SSRIs and SNRIs. The safety profile is the same as in depression: liver-enzyme monitoring is mandatory before treatment and at 3, 6, 12, and 24 weeks, and the drug is contraindicated in active liver disease. Whether to use it is an individual decision when standard options have failed.

Marketing claims without evidence base

The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.

How to read tiers A–F

Evidence tiers belong to the drug-indication pair, not to the drug as a whole: the same substance can be A for one condition and F for another.

AStrong evidence – first or second line in international guidelines
BRecommended in selected cases
CStudy data contradict each other
DBenefit not proven, no documented harm
FDocumented harm, or risk without benefit