Can a patient with Parkinson's disease and severe anxiety be prescribed lorazepam (Ativan)?

Can Ativan (Lorazepam) Be Prescribed for Severe Anxiety in Parkinson's Disease?

Lorazepam should generally be avoided in Parkinson's disease patients with severe anxiety, even though no absolute contraindication exists, because benzodiazepines significantly increase fall risk in this already high-risk population and lack evidence of efficacy for anxiety in PD. 1, 2

Evidence Against Benzodiazepine Use in Parkinson's Disease

• Only one study has examined benzodiazepines for anxiety treatment in PD, and the conclusion was that benzodiazepines cannot be recommended because they increase the risk of falling 1
• Parkinson's patients already have substantially elevated fall risk due to postural instability, bradykinesia, and orthostatic hypotension—adding a benzodiazepine compounds this danger 1
• Benzodiazepines can worsen cognitive function in elderly patients, and PD patients are at higher baseline risk for cognitive decline 3, 4
• In elderly populations generally, benzodiazepines increase delirium incidence and duration, and cause paradoxical agitation in approximately 10% of patients 4

Preferred Pharmacological Alternatives for Anxiety in PD

First-Line: SSRIs

• Selective serotonin reuptake inhibitors (SSRIs) are the preferred first-line treatment for anxiety in Parkinson's disease based on modest evidence of benefit and favorable side effect profiles 1, 2
• Sertraline or citalopram are reasonable choices, starting at low doses (sertraline 25-50 mg daily, citalopram 10 mg daily) and titrating as tolerated 3, 2
• SSRIs have demonstrated modest effect sizes in treating anxiety in PD, though the evidence base remains limited 1
• SSRIs can be used for both depression and anxiety, which commonly co-occur in PD (anxiety coexists with depression in many PD patients) 5, 2

Alternative: Clonazepam (If SSRI Insufficient)

• Clonazepam may be considered if an SSRI is insufficient or if the patient also has REM sleep behavior disorder, which is common in PD 2
• Clonazepam has a longer half-life than lorazepam, providing more sustained anxiolysis without frequent dosing 3, 2
• However, clonazepam still carries fall risk and should be used at the lowest effective dose 4

Other Options

• Mirtazapine can be chosen if insomnia or weight loss accompanies anxiety 2
• Venlafaxine (SNRI) may be used in patients who do not tolerate SSRIs 2
• Tricyclic antidepressants showed modest benefit in one trial but cause additional anticholinergic side effects that can worsen cognition and motor symptoms in PD 1, 6

Critical Consideration: Anxiety Related to Motor Fluctuations

• Anxiety in PD is often associated with "off-periods" (when dopaminergic medication wears off) and improves with L-Dopa, especially in patients with high baseline anxiety levels 1
• Optimizing dopaminergic therapy to decrease off-periods is essential for managing anxiety in patients with motor fluctuations 1, 7
• Patients with comorbid motor fluctuations are more likely to require treatment for anxiety (odds ratio 3.65) 7
• Consider controlled-release levodopa preparations or adjusting dopamine agonist dosing before adding anxiolytics 6

Important Caveats About Medication Interactions

• Avoid combining SSRIs with MAO-B inhibitors like selegiline due to risk of serotonin syndrome, though this combination can be used with caution 6
• Some case reports suggest SSRIs may worsen parkinsonian motor symptoms in isolated cases, though this is uncommon 6
• Anticholinergic medications should be discontinued if cognitive decline is present, as they may worsen mental status 6

The Reality of Undertreatment

• Over 50% of non-depressed PD patients with clinically significant anxiety receive no pharmacological treatment 7
• Patients with anxiety alone (without comorbid depression) are significantly less likely to be treated than those with both conditions (odds ratio 8.33 for treatment if depression is present) 7
• This suggests anxiety in PD is under-recognized and undertreated, but the solution is not benzodiazepines—it is better recognition and use of SSRIs 7

Practical Algorithm

1. Optimize dopaminergic therapy first: Reduce off-periods with controlled-release levodopa or adjust dopamine agonist timing 1, 6
2. If anxiety persists despite optimized motor control: Initiate an SSRI (sertraline 25-50 mg or citalopram 10 mg daily) 1, 2
3. If SSRI is insufficient after 4-6 weeks at adequate dose: Consider adding low-dose clonazepam (0.25-0.5 mg) rather than lorazepam, particularly if REM sleep behavior disorder is present 2
4. Reserve short-acting benzodiazepines like lorazepam only for rare, acute situational anxiety (e.g., MRI claustrophobia), not for chronic anxiety management 2
5. Monitor closely for falls, cognitive changes, and motor symptom worsening with any psychotropic medication 1, 6

Why the Evidence Base Is Weak

• No randomized controlled trials have been conducted with anxiety as the primary outcome measure in PD 1
• Most treatment recommendations are extrapolated from general population data and clinical experience 2
• The two trials showing benefit of antidepressants for anxiety in PD had modest effect sizes 1
• Further clinical studies are urgently needed to establish evidence-based treatment guidelines 1, 5