What are the potential side effects of Lyrica (pregabalin) in a patient with social anxiety and attachment anxiety, particularly one with a history of failing or not tolerating selective serotonin reuptake inhibitors (SSRIs)?

Side Effects of Lyrica (Pregabalin)

Lyrica (pregabalin) most commonly causes dizziness and somnolence, which are dose-dependent and typically develop tolerance within a few weeks, though serious risks include life-threatening allergic reactions, respiratory depression (especially with concomitant CNS depressants), and suicidal ideation. 1

Most Common Side Effects

Neurological Effects (Most Frequent)

• Dizziness occurs in 21-32% of patients (compared to 5-11% with placebo), with higher rates at doses of 300-600 mg/day 1
• Somnolence affects 12-22% of patients (versus 3-11% with placebo), increasing with dose escalation 1
• Ataxia develops in 3-15% of patients, particularly at higher doses 1
• Cognitive impairment ("thinking abnormal") occurs in 2-8% of patients, manifesting as difficulty with concentration, attention, cognition, language problems, and slowed thinking 1
• Confusion affects 2-4% of patients 1
• Other neurological effects include tremor, incoordination, abnormal gait, amnesia, and speech disorders 1

Metabolic and Physical Effects

• Weight gain occurs in 4-12% of patients (versus 0-1% with placebo), with dose-dependent increases 1
• Peripheral edema develops in 5-9% of patients (compared to 2% with placebo) 1
• Increased appetite affects 5% of patients 1

Visual Disturbances

• Blurred vision occurs in 4-10% of patients (versus 2-4% with placebo) 1
• Diplopia (double vision) affects 2-9% of patients 1

Other Common Effects

• Dry mouth (4%), constipation (4%), dyspnea (2%) 1
• Euphoria occurs in 2% of patients, reflecting the drug's controlled substance status 1

Serious and Life-Threatening Side Effects

Allergic Reactions (Immediate Action Required)

The FDA mandates warnings for serious, potentially life-threatening allergic reactions requiring immediate discontinuation 1:

• Swelling of face, mouth, lips, gums, tongue, throat, or neck (angioedema)
• Trouble breathing
• Rash, hives, or blisters

Respiratory Depression

Serious breathing problems can occur when pregabalin is combined with other CNS depressants or in patients with pre-existing respiratory conditions 1. This represents a critical safety concern requiring vigilant monitoring, especially during dose initiation or escalation 1.

Suicidal Ideation

Like other antiepileptic drugs, pregabalin carries a risk of suicidal thoughts or actions in approximately 1 in 500 patients 1. Warning signs include:

• New or worsening depression, anxiety, agitation, or restlessness
• Panic attacks, insomnia, irritability
• Acting aggressive, angry, or violent
• Thoughts about suicide or dying 1

Patients should not abruptly discontinue pregabalin if suicidal thoughts emerge; instead, contact a healthcare provider immediately, as sudden cessation can cause serious problems 1.

Cardiovascular Concerns

Peripheral edema can be particularly problematic for patients with heart failure, requiring careful monitoring 1.

Discontinuation and Withdrawal

Treatment Discontinuation Rates

• 14-15% of patients discontinue pregabalin due to adverse reactions (compared to 6-7% with placebo) 1
• The most common reasons for discontinuation are dizziness (4-6%), somnolence (3%), and ataxia (4%) 1

Withdrawal Management

Withdrawal symptoms during gradual tapering (over one week) are typically mild and similar after both acute and chronic administration 2. However, abrupt discontinuation should be avoided 1.

Dose-Dependent Effects

Side effects demonstrate clear dose-response relationships, with significantly higher rates at 600 mg/day compared to lower doses 1, 2:

• Dizziness: 8% at 75 mg/day versus 29-37% at 600 mg/day 1
• Somnolence: 4-8% at 75 mg/day versus 16-25% at 600 mg/day 1
• Weight gain: 0% at 75 mg/day versus 6-16% at 600 mg/day 1

Tolerance Development

Tolerance to dizziness and somnolence typically develops within a few weeks of treatment, improving the overall tolerability profile with continued use 2, 3.

Context for Social Anxiety Treatment

For patients with social anxiety who have failed SSRIs, pregabalin at doses of 450-600 mg/day represents an evidence-based alternative 4, 5, 6, 7. The Canadian Clinical Practice Guideline lists pregabalin as a first-line option for social anxiety disorder 4. However, the 150 mg/day dose was not significantly better than placebo in clinical trials 5, necessitating higher doses for therapeutic effect.

Pregabalin demonstrates faster onset of anxiolytic effects (within one week) compared to SSRIs/SNRIs, similar to benzodiazepines but without the same dependence liability 2, 3. The drug shows less cognitive and psychomotor impairment than benzodiazepines like alprazolam 2.

Critical Monitoring Parameters

• Assess for increased sleepiness or decreased breathing when starting or increasing doses 1
• Monitor for emergence of suicidal thoughts, especially in the first weeks of treatment 1
• Watch for signs of allergic reactions requiring immediate discontinuation 1
• Evaluate peripheral edema, particularly in patients with cardiac conditions 1
• Consider gradual dose titration to minimize initial dizziness and somnolence 2