Why are benzodiazepines prescribed to adult patients with Attention Deficit Hyperactivity Disorder (ADHD) or depression who experience significant anxiety or agitation?

Why Benzodiazepines Are Prescribed

Benzodiazepines are prescribed primarily for their anxiolytic, sedative, hypnotic, anticonvulsant, and amnestic effects through GABA-A receptor activation, making them effective for acute anxiety, agitation, insomnia, seizures, and muscle spasticity—but they should be limited to the shortest duration possible (ideally 2-4 weeks maximum) due to risks of dependence, tolerance, and withdrawal. 1, 2

Core Therapeutic Mechanisms and Effects

Benzodiazepines activate γ-aminobutyric acid A (GABA) neuronal receptors in the brain, the primary CNS inhibitory neurotransmitter system. 1 This produces:

• Anxiolytic effects - reducing pathological anxiety 1, 3
• Sedative/hypnotic effects - inducing sleep and sedation 1, 2
• Anticonvulsant effects - controlling seizures 1, 3
• Amnestic effects - which extend beyond their sedative properties 1
• Muscle relaxant effects - reducing spasticity from CNS pathology 4

Critically, benzodiazepines have NO analgesic activity, so they should never be used for pain management alone. 1

Primary Clinical Indications

Acute Anxiety and Agitation

For acute anxiety or agitation, lorazepam is the preferred agent due to its fast onset, rapid and complete absorption, no active metabolites, and predictable pharmacokinetics. 2 The combination of a benzodiazepine plus an antipsychotic is frequently recommended for acutely agitated patients. 1, 2

• Benzodiazepines are indicated for acute stress reactions, episodic anxiety, fluctuations in generalized anxiety, and initial treatment for severe panic 3
• Diazepam is usually the drug of choice for anxiety when given in single doses or very short courses (1-7 days), though courses should rarely exceed 2-4 weeks 3

Insomnia Management

Cognitive behavioral therapy for insomnia (CBT-I) should be the initial intervention, NOT benzodiazepines. 2 When pharmacotherapy is necessary:

• For sleep-onset insomnia: Use short-acting agents like triazolam (0.125-0.25 mg) 2
• For sleep-maintenance insomnia: Use intermediate-acting agents like temazepam (7.5-30 mg, start 7.5 mg in elderly) 2
• Prescriptions should be limited to a few days, occasional/intermittent use, or courses not exceeding 2 weeks 3

Other Established Uses

• Epilepsy: Diazepam, clonazepam, and clobazam for seizure control 3
• Anesthesia: Midazolam for procedural sedation 3
• ICU sedation: For managing agitation in critically ill patients 1
• Acute psychoses: Occasionally used as adjunctive treatment 3
• Alcohol withdrawal: Managing delirium tremens 5

Critical Safety Considerations and Contraindications

Respiratory and Cardiovascular Risks

Benzodiazepines cause respiratory depression and systemic hypotension, especially when combined with opioids or other CNS depressants. 1 This risk is dramatically increased in:

• Patients with baseline respiratory insufficiency 1
• Patients with cardiovascular instability 1
• The combination of benzodiazepines with opioids should be avoided due to dangerous synergistic respiratory depression 2

Dependence, Tolerance, and Withdrawal

Even taking benzodiazepines as prescribed puts patients at risk for abuse, misuse, and addiction. 6 Key warnings include:

• Physical dependence develops from continued therapy, manifesting as withdrawal symptoms after abrupt discontinuation 6
• Tolerance develops after some weeks of therapy, even at therapeutic doses 5
• Abrupt discontinuation can precipitate life-threatening withdrawal reactions including seizures 6
• Withdrawal symptoms include anxiety, tremor, insomnia, and rarely seizures or psychosis 2, 6
• Protracted withdrawal syndrome can persist for weeks to more than 12 months 6

Special Population Warnings

Benzodiazepines should be avoided entirely in elderly patients due to high risks of dependence, cognitive impairment, and falls. 2 When unavoidable:

• Start with half the standard adult dose 2
• Prefer agents with shorter half-lives and no active metabolites: lorazepam, oxazepam, temazepam 2
• Elderly patients are significantly more sensitive to sedative effects 1
• Long-acting benzodiazepines like diazepam should be avoided in elderly patients with liver disease due to accumulation of active metabolites causing prolonged sedation and delirium 2

Contraindications and Cautions

• Avoid in patients with substance abuse history 2
• Exercise caution in depression, respiratory compromise, or hepatic/cardiac disease 2
• Avoid use in pregnancy and nursing 2
• Benzodiazepine clearance is reduced in hepatic dysfunction, renal failure, and elderly patients 1

Specific Context: Depression and ADHD

In patients with depression, chronic benzodiazepine use is associated with poorer depressive outcomes and functional status. 7 The neuroadaptive consequences of long-term use—including decreased GABA and monoaminergic function and interference with neurogenesis—may oppose antidepressant mechanisms. 7

However, short-term combination therapy (antidepressant plus benzodiazepine) for up to 4 weeks shows 38-63% greater response rates and 37% lower dropout rates compared to antidepressant alone. 8 None of the trials followed patients beyond 8 weeks, and there are no efficacy trials published beyond 8 weeks for continuous benzodiazepine use. 7

For ADHD patients with comorbid anxiety, benzodiazepines are NOT first-line treatment—they provide no benefit for core ADHD symptoms and carry significant risks of dependence and cognitive impairment that may worsen attention deficits.

Dosing and Duration Principles

The fundamental principle: Use the lowest effective dose for the shortest possible duration, ideally no more than 2-4 weeks. 2, 3

• Dose on an empty stomach to maximize effectiveness 2
• To reduce withdrawal risk, use gradual taper when discontinuing 6
• Patients at increased withdrawal risk include those on higher dosages and longer durations 6
• Long-term prescription is occasionally required for certain patients but should be exceptional 3

Common Pitfalls to Avoid

• Never use benzodiazepines as monotherapy for depression—they have little to no antidepressive effects 8
• Avoid combining with alcohol or other CNS depressants due to increased accident risk and respiratory depression 2
• Do not abruptly discontinue—always taper gradually 6
• Avoid prescribing alprazolam for long-term use—it is not recommended in the UK despite widespread US use 3
• Do not use potent, short-acting agents like triazolam chronically—they carry greater risks of adverse effects 3