What should I give someone with complaints of irritability?

Management of Irritability

The approach to treating irritability depends critically on identifying the underlying cause: if irritability is a symptom of a psychiatric disorder (depression, anxiety, DMDD), treat the primary condition; if it represents an isolated mood disturbance or organic irritability syndrome, start with an SSRI like sertraline or consider valproate as first-line therapy.

Initial Assessment and Differential Diagnosis

Before initiating treatment, you must determine whether irritability is:

• A symptom of an underlying psychiatric disorder (depression, anxiety, bipolar disorder, ADHD, personality disorders, substance abuse) - irritability appears as a diagnostic or associated feature in 15 different DSM disorders 1
• An isolated mood disturbance characterized by low frustration tolerance, hostility, impulsivity, and aggression 1
• Organic irritability syndrome - persistent irritable mood with hyperactivity and/or disrupted sleep, lacking the typical hyposomnia and pressured speech of mania, often associated with CNS dysfunction 1

Key clinical features to assess:

• Frequency, intensity, and duration of irritable episodes - most people experience irritability 1-2 times per week lasting approximately 30 minutes 2
• Presence of comorbid psychiatric symptoms (mood changes, anxiety, psychosis, sleep disturbance) 3
• Physiological/biological/internal aspects and triggers 2
• Impact on educational, financial, and social functioning 4

Treatment Algorithm

Step 1: Treat Underlying Psychiatric Disorder (If Present)

When irritability is secondary to a psychiatric condition, the choice of medication depends on the primary diagnosis:

• For depression with irritability: Start with an SSRI (sertraline preferred) 3
• For psychotic disorders with irritability: Use atypical antipsychotics as first-line 3
• For disruptive mood dysregulation disorder (DMDD) in children/adolescents: Consider parent management training (PMT) or cognitive behavioral therapy (CBT) as first-line psychological interventions 5

Step 2: First-Line Pharmacotherapy for Primary Irritability

Start with one of these options:

• SSRI (sertraline preferred) - has mild side effect profile and addresses the underlying serotonergic dysregulation of dopaminergic activity that characterizes pathological irritability 3, 1
• Valproate (mood stabilizer) - alternative first-line option with mild side effect profile 3

Step 3: If Insufficient Response

Switch between the two first-line medications:

• If started on SSRI, switch to valproate 3
• If started on valproate, switch to SSRI 3

Step 4: Second-Line Options

If first-line treatments fail, consider:

• Low-dose atypical antipsychotic (preferably dosed twice daily) - addresses dopamine receptor antagonism 3, 1
• Buspirone - can be used as monotherapy or add-on therapy 3

Step 5: Third-Line Options (Only When Earlier Treatments Ineffective)

• Other mood stabilizers (lithium, carbamazepine) - all have been reported effective but lack controlled trial data 1, 3
• Beta-adrenergic receptor antagonists 3

Avoid acetylcholinesterase inhibitors - results are unclear and not recommended for irritability treatment 3

Non-Pharmacological Interventions

Psychological treatments should be considered alongside or before pharmacotherapy:

• Cognitive behavioral therapy (CBT) - most supported psychological treatment for irritability 5
• Exposure-based CBT techniques - promising approach based on pathophysiological findings showing bias toward threatening stimuli 5
• Interpretation bias training (IBT) - currently under investigation 5
• Behavioral therapy to reduce stress levels 3
• Relaxation and recreational activities - address emotional and physiological coping mechanisms unique to irritability 2

Critical Pitfalls to Avoid

Common mistakes in managing irritability:

• Ignoring irritability as "just behavioral" - it represents a mood problem with substantial morbidity and impairment requiring treatment 5
• Failing to identify comorbid psychiatric disorders - irritability may be secondary to conditions requiring different treatment approaches 3
• Overlooking drug-drug interactions - particularly important in patients taking multiple medications 3
• Equating irritability with anger alone - irritability has distinct physiological/biological/internal aspects that differentiate it from pure anger 2

Special Considerations

The pathophysiology of irritability involves:

• Limbic system dysfunction with central dysregulation of serotonergic inhibition of dopaminergic activity 1
• Aberrant reward processing and bias toward threatening stimuli 5

Gender and cultural factors:

• Women report longer duration of irritable episodes than men 2
• Duration varies by geographic region, though generalizations should be interpreted cautiously 2