Intervention: Duloxetine
Trial phase: Phase 4
ATC code: N06AX21
SMILES: CNCC[C@H](Oc1cccc2ccccc12)c1cccs1
Sex: All
Age groups: Older Adult
Healthy volunteers: No
Participants at risk: 151
Group description: 30 to 120 milligrams (mg) administered orally, once daily for 10 weeks. Starting dose, 30-mg capsule, once daily for 2 weeks, with option to increase dose (30-mg increments) at Weeks 2, 4, and 7. If participant's Clinical Global Impression of Improvement (CGI-Improvement) Score was ≥3 (minimal improvement, no change, or worse) at Week 2, 4, or 7, the dose was required to be increased by 30 mg. At end of 10-week treatment period, participants had choice to enter 2-week taper period or begin active treatment (duloxetine or other).

Optional taper period: Dosing was dependent on the participant's final dosage during the treatment period. Participants taking duloxetine 120 or 90 mg once daily received duloxetine 60 mg once daily for 1 week followed by 30 mg once daily for 1 week. Participants taking duloxetine 60 mg once daily received duloxetine 30 mg once daily for 1 week followed by placebo for 1 week. Participants taking duloxetine 30 mg once daily received placebo for 2 weeks.
Eligibility criteria:
Inclusion Criteria:

Have GAD based on diagnostic criteria and not suffer from an adjustment disorder or anxiety disorder not otherwise specified. Symptoms of GAD should not be situational in nature.
Have a Mini Mental State Examination (MMSE) score of at least 24 at screening.
Have a Clinical Global Impressions of Severity (CGI-Severity) score of greater than or equal to 4 at screening and randomization.
Have a Covi Anxiety Scale (CAS) score of greater than or equal to 9, no item in the Raskin Depression Scale (RDS) may be >3, and the CAS score must be greater than the RDS at screening.
Have a Hospital Anxiety and Depression Scale (HADS) anxiety subscale score of greater than or equal to 10 at screening.
Have a degree of understanding such that the participant can communicate intelligibly with the investigator and study coordinator.
Are judged to be reliable to keep all appointments and able to swallow all required medication without opening or crushing.

Exclusion Criteria:

Have any current and primary Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-Text Revised (DSM-IV TR) Axis I diagnosis other than GAD, with the exception of comorbid social phobia or specific phobia.

major depressive disorder (MDD) within the past 6 months, or
panic disorder, posttraumatic stress disorder (PTSD), or an eating disorder within the past year, or
obsessive compulsive disorder (OCD), bipolar affective disorder, psychosis, factitious disorder, or somatoform disorders during their lifetime.
The presence of an Axis II disorder, or history of antisocial behavior, or participants who, in the opinion of the investigator, are poor medical or psychiatric risks for study compliance.
Have organic mental disorder or mental retardation diagnosis.
Use of benzodiazepine within 14 days prior to randomization.
Are judged clinically to be at serious risk of harm to self or others.
Are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an off-label use of an investigational drug or device, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study.
Have previously completed or withdrawn from this study or any other study investigating duloxetine or have previously been treated with duloxetine within the past year or participants with a lack of response or intolerability to duloxetine (for any approved indication) at a clinically appropriate dose for a minimum of 4 weeks.
Have a history of alcohol or any psychoactive substance abuse or dependence within the past 6 months.
Excessively use caffeine, in the opinion of the investigator.
Have a positive urine drug screen (UDS) for any substances of abuse at screening.
Have a serious medical illness.
Have any acute liver injury or severe cirrhosis.
Have an abnormal thyroid-stimulating hormone (TSH) concentrations.
Have initiated psychotherapy or changed intensity of psychotherapy or other non-drug therapies (such as acupuncture or hypnosis) within 6 weeks prior to enrollment or at any time during the study.
Have taken any excluded medication within 7 days prior to randomization.
Have been treated with a monoamine oxidase inhibitor (MAOI) or fluoxetine within 30 days of randomization or potentially need to use an MAOI during the study or within 5 days of discontinuation of study drug.
Exhibit a lack of response of the current episode of GAD to 2 or more adequate trials of antidepressants, benzodiazepines, or other anxiolytics at a clinically appropriate dose for a minimum of 4 weeks.
Have a history of severe allergies, hypersensitivity to duloxetine or to any of the inactive ingredients; multiple adverse drug reactions; transcranial magnetic stimulation (TMS); history of seizures; or history of psychosurgery or electroconvulsive therapy (ECT) within 12 months.
Have discontinued hormone replacement therapy within the previous 3 months.
Have uncontrolled narrow-angle glaucoma.