What is the appropriate workup and treatment for a 34-year-old male presenting with symptoms of anger and agitation?

Workup and Treatment for a 34-Year-Old Male with Anger and Agitation

Your primary goal is to identify and treat reversible medical and psychiatric causes before attributing symptoms to a primary behavioral disorder, as undiagnosed medical conditions disproportionately contribute to agitation and can be life-threatening if missed. 1

Initial Assessment: Rule Out Medical Causes First

The workup must systematically exclude organic etiologies, as agitation is often a nonspecific symptom of underlying pathophysiology rather than a primary psychiatric condition 2:

Medical History and Physical Examination

• Medication review: Bring in all prescription bottles, over-the-counter drugs, and supplements to assess for anticholinergic agents, sympathomimetics, or drug interactions that can cause or worsen agitation 1
• Substance use screening: Evaluate for alcohol, stimulants, or withdrawal states, as intoxication can mimic psychiatric symptoms 1
• Pain assessment: Undiagnosed pain is a disproportionate contributor to agitation, particularly in patients who may have difficulty communicating discomfort 1
• Vital signs: Abnormal vital signs suggest medical illness requiring immediate attention 1

Laboratory Workup

Order the following to identify reversible causes 1:

• Complete blood count with differential (to detect infection, anemia)
• Comprehensive metabolic panel including glucose and electrolytes (to identify metabolic derangements)
• Urinalysis (to rule out urinary tract infection)
• Thyroid function tests (hyperthyroidism can present with agitation) 3
• Consider toxicology screen if substance use is suspected 1

Neurological Considerations

• Assess for head injury, seizure disorder, or other organic brain pathology if history or examination suggests neurological involvement 3, 4
• Consider EEG if episodic rage attacks with abnormal neurological findings are present 4

Psychiatric Differential Diagnosis

Once medical causes are addressed, consider psychiatric etiologies 5, 3:

Primary Psychiatric Disorders Associated with Anger/Agitation

• Mood disorders: Bipolar disorder (particularly mixed or manic episodes), major depressive disorder with irritability 3, 4
• Anxiety disorders: Generalized anxiety disorder, panic disorder 2
• Substance use disorders: Including alcohol use disorder 1
• Personality disorders: Particularly antisocial, borderline, or intermittent explosive disorder 3, 4
• Attention-deficit/hyperactivity disorder: Can present with irritability and emotional dysregulation in adults 3
• Psychotic disorders: Schizophrenia or schizoaffective disorder with agitation 1, 6

Screening for Bipolar Disorder is Critical

Before initiating antidepressant therapy, you must screen for bipolar disorder risk, as treating unrecognized bipolar depression with antidepressants alone may precipitate manic or mixed episodes. 7 Obtain detailed psychiatric history including family history of bipolar disorder, suicide, and depression 7.

Characterize the Agitation Using the DICE Approach

Use structured questioning to understand the context 1:

DESCRIBE the Behavior

• Ask the wife to describe specific incidents "as if in a movie" - what exactly happens, when, and how often 1
• Identify antecedents (what triggers the anger), the behavior itself, and consequences 1
• Determine what aspect is most distressing to the patient and spouse, and establish treatment goals 1
• Assess severity: Is there verbal aggression only, or physical violence? Is there risk to self or others? 1, 5

INVESTIGATE Underlying Causes

Beyond medical workup, explore 1:

• Patient factors: Current stressors, sleep deprivation, chronic pain, undiagnosed psychiatric comorbidity
• Environmental factors: Work stress, relationship conflicts, financial pressures
• Cognitive function: Is there evidence of cognitive impairment that might suggest early dementia or other neurocognitive disorder?

Treatment Algorithm

Non-Pharmacological Interventions (First-Line)

Attempt verbal de-escalation and behavioral interventions before pharmacological management whenever possible. 1, 8

• Individual psychotherapy (cognitive-behavioral therapy for anger management)
• Couples counseling to address relationship dynamics and communication patterns
• Stress reduction techniques and lifestyle modifications
• Address modifiable triggers identified in the DESCRIBE phase 1

Pharmacological Treatment Based on Underlying Diagnosis

If Underlying Mood Disorder (Depression/Bipolar)

• For unipolar depression with irritability: Consider SSRI such as sertraline, but monitor closely for emergence of agitation, hostility, or aggressiveness, especially in the first few weeks 7
• Warning: SSRIs can paradoxically cause agitation, irritability, hostility, and aggressiveness, particularly early in treatment 7. Families should monitor daily and report immediately if symptoms worsen 7
• For bipolar disorder: Mood stabilizers (lithium, valproate, carbamazepine) are first-line; lithium has established efficacy for irritability and anger outbursts in bipolar patients 4

If Pathologic Aggression Without Clear Psychiatric Diagnosis

The evidence supports several options 4:

• Lithium: Effective for explosive behavior and aggression in various populations; would be first choice if bipolar features present 4
• Anticonvulsants: Valproate or carbamazepine have evidence for treating pathologic aggression in personality disorders and organic brain syndrome 4
• Beta-blockers: Propranolol effective for reducing violent behavior across multiple conditions, though limited by hypotension and bradycardia at higher doses 4
• Atypical antipsychotics: Risperidone has documented effectiveness in aggressive behavior, though typically reserved for more severe cases 3, 4

If Acute Severe Agitation Requiring Immediate Control

This scenario is less likely in outpatient setting, but if patient presents with dangerous agitation 1, 8:

• Benzodiazepines: Lorazepam 2-4 mg PO/IM is as effective as haloperidol and may be preferred if medical etiology suspected 1, 8
• Haloperidol: 5 mg has extensive evidence base for acute agitation 1, 8
• Combination therapy: Lorazepam plus haloperidol may produce more rapid sedation than monotherapy 8

Common Pitfalls to Avoid

1. Do not prescribe antidepressants without screening for bipolar disorder - this can precipitate mania 7
2. Do not use antipsychotics in anticholinergic toxicity - they can worsen agitation due to their own anticholinergic effects 1
3. Do not rely solely on blood alcohol level - assess cognitive function individually if substance use is involved 1
4. Do not assume psychiatric cause without medical workup - reversible medical causes must be identified first 1
5. Monitor closely if starting SSRIs - agitation and hostility can emerge or worsen, particularly in first weeks of treatment 7

Follow-Up and Monitoring

• Schedule close follow-up within 1-2 weeks of initiating any medication 7
• Educate patient and spouse about warning signs of worsening (increased agitation, hostility, impulsivity) and instruct them to report immediately 7
• Consider psychiatric referral if symptoms are severe, refractory to initial treatment, or if diagnostic uncertainty exists 5
• Reassess regularly for treatment response and medication side effects 7