Pharmacotherapy of generalized anxiety disorder: focus and update on pregabalin

Abstract

Generalized anxiety disorder (GAD) is one of the most common psychiatric disorders and clinically characterized by both psychological anxiety and somatic symptoms (muscular tension and autonomic symptoms). Next to serotonergic antidepressants, the Ca²⁺ channel α₂δ ligand pregabalin is an approved first-line treatment of GAD in many countries. Pregabalin is considered effective against psychological and somatic anxiety symptoms alike. However, occurrence of discontinuation syndromes and a growing number of reports regarding abuse or dependence during the last years are concerns, particularly in patients with a history of addictive behavior. Here we review key issues of GAD and the pharmacology and pharmacokinetics of pregabalin. Above all, we evaluate evidence from available randomized placebo-controlled as well as head-to-head clinical trials with other drugs regarding its efficacy and safety in the GAD treatment.

Keywords::

• anxiolytic
• drug therapy
• generalized anxiety disorder
• pregabalin
• randomized controlled trials

Financial & competing interests disclosure

C Lange-Asschenfeldt has received lecture fees and/or travel support from Novartis, AstraZeneca and Servier, and research funding from Pfizer and Bristol Myers-Squibb. G Kojda has received lecture fees from Boehringer and Mundipharma, consulting fees from Pfizer and research funding from Actavis, Schwarz Pharma, Pfizer and Shire. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Generalized anxiety disorder (GAD) is characterized by persistent, excessive and unfocused worry or anxiety, usually accompanied by muscular tension, restlessness and autonomic symptoms such as palpitations, abdominal complaints, sweating, nausea and dry mouth.

• Therapeutic options include psychological and drug treatment. Of the latter, cognitive behavioral therapy is best studied and most widely used. Antidepressants, anxiolytics (above all, benzodiazepines), anticonvulsants and second generation antipsychotics have all been evaluated for the treatment of GAD.

• Pregabalin was approved by the European Medicines Agency in March 2006 for the treatment of GAD. According to current international guidelines, pregabalin, selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors are recommended as first-line treatment for GAD.

• Pregabalin was significantly superior to placebo in all clinical trials as assessed by a significant decrease in the Hamilton Rating Scale for Anxiety. However, it is not more effective than the benzodiazepines alprazolam or lorazepam and venlafaxine.

• Pregabalin showed significant effectiveness in reducing both somatic and psychological anxiety symptoms.

• Side effects of pregabalin are usually considered mild to moderate. Dizziness and somnolence, headache, dry mouth, nausea and weight gain were most common and frequent side effects.

• There is a risk of withdrawal symptoms after cessation of pregabalin treatment, especially in a dose ≥150 mg/d. Withdrawal symptoms can be anxiety, restlessness, irritability, nervousness, insomnia or rebound effects.

• Current recommendations of the World Federation of Societies of Biological Psychiatry have evaluated escitalopram, paroxetine, duloxetine, venlafaxine and pregabalin with the highest level of evidence.