What is the appropriate work‑up and first‑line psychiatric treatment for a patient presenting with derealization?

Psychiatric Treatment for Derealization

For a patient presenting with derealization, first rule out delirium and other medical causes through targeted workup (orientation testing, vital signs, basic labs, and selective neuroimaging based on red flags), then initiate trauma-focused psychotherapy as the primary treatment, with SSRIs or lamotrigine as adjunctive pharmacotherapy for comorbid depression or anxiety. 1, 2, 3

Initial Diagnostic Workup

Immediate Assessment to Rule Out Delirium

• Test orientation and attention first – ask the patient the current date, location, and time; have them spell "WORLD" backwards or perform serial sevens (100 – 7,93 – 7) to detect fluctuating consciousness that signals delirium rather than primary derealization 4
• Assess for acute onset over hours-to-days – delirium presents with rapid symptom development and waxing-waning consciousness, whereas depersonalization-derealization disorder (DPD) develops gradually over weeks-to-months 4, 1
• Missing delirium doubles mortality risk, making this the most critical first step 4

Essential Laboratory Testing

• Complete blood count to evaluate for infection or hematologic abnormalities 5
• Comprehensive metabolic panel to assess electrolyte imbalances, renal and liver function 5
• Thyroid function tests to rule out thyroid disorders 5
• Blood glucose measurement to exclude hypo/hyperglycemia 5
• Urinalysis to screen for urinary tract infections 5
• Toxicology screen to assess for substance intoxication or withdrawal, particularly cannabis and classic psychedelics which commonly precipitate persistent derealization 1, 5

Selective Neuroimaging Indications

• Obtain brain MRI (or CT if MRI unavailable) only when specific red flags are present: focal neurological deficits, recent head trauma, new-onset seizures, signs of increased intracranial pressure, or unexplained altered mental status despite initial workup 6, 4
• Do not routinely image patients with isolated derealization symptoms and no neurological findings – the yield is extremely low and delays appropriate psychiatric treatment 6

Distinguishing Primary Derealization from Secondary Causes

Key Diagnostic Features of Primary DPD

• Consciousness and awareness remain completely intact – patients can describe their symptoms clearly and maintain orientation, unlike delirium where consciousness fluctuates 6, 4, 1
• Symptoms persist most of the day for months, not hours-to-days 1, 7
• High comorbidity with depression, anxiety disorders, and personality disorders – screen systematically for these conditions 1, 8, 7
• Strong association with early attachment trauma and emotional avoidance – obtain detailed trauma history 1, 2

Substance-Induced Derealization

• If psychotic symptoms persist longer than one week after documented detoxification, consider primary DPD rather than substance-induced disorder 9
• Cannabis and classic psychedelics frequently precipitate DPD in vulnerable individuals by mobilizing anxiety-laden unconscious emotions from early trauma 1
• The drug acts as a catalyst, not the primary cause – DPD results from avoidance of aversive emotional states and functional alterations of brain networks, not organic brain damage 1

First-Line Treatment: Trauma-Focused Psychotherapy

Long-term psychotherapy of 50-100 sessions is required to achieve remission – this is the primary evidence-based treatment for DPD 1, 3

Core Psychotherapy Components

• Psychoeducation about the nature of DPD – explain that derealization is a dissociative response to overwhelming emotions, not permanent brain damage from drug use 1, 2
• Challenge false causal attributions to external causes (such as drug intake) that erode self-efficacy and hinder awareness of emotional conflicts 1
• Help patients experience and process emotions adaptively rather than avoiding them through dissociation 1, 2
• Address early attachment traumas that underlie the disorder 1, 2

Specific Psychotherapy Modalities

• Trauma-focused cognitive-behavioral therapy 2, 3
• Psychodynamic psychotherapy targeting emotional avoidance 1, 2
• Grounding techniques and mindfulness-based interventions 2, 3

Adjunctive Pharmacotherapy

No medication is FDA-approved specifically for DPD, but pharmacotherapy can target comorbid conditions and reduce symptom severity 3

Evidence-Based Medication Options

• SSRIs (fluoxetine, escitalopram, sertraline) – for comorbid depression and anxiety, which are present in the majority of DPD patients 3, 8, 7
• Lamotrigine – emerging evidence suggests benefit for core derealization symptoms, particularly when combined with psychotherapy 3
• Avoid benzodiazepines as monotherapy – they do not address the underlying emotional avoidance and may worsen dissociation 6

Medication Selection Algorithm

1. If comorbid depression or anxiety is present (screen with PHQ-2 and GAD-2), initiate an SSRI 8, 7
2. If derealization symptoms persist despite psychotherapy and SSRI treatment, consider adding lamotrigine 3
3. Titrate doses to optimal relief while monitoring for side effects 3

Prognostic Factors and Monitoring

• Derealization symptoms are independent risk factors for persistence or incidence of depression and anxiety – each point increment on derealization scales increases risk of elevated depression/anxiety symptoms by 21% at 2.5-year follow-up 8
• Symptoms of derealization indicate disease severity and negatively predict therapy outcome when left untreated 7
• Reassess regularly – patients require long-term follow-up to monitor treatment response and adjust interventions 1, 3

Critical Pitfalls to Avoid

• Do not attribute persistent derealization solely to past drug use – this reductionist conclusion leads to false illness perceptions, hinders awareness of emotional conflicts, and erodes patient self-efficacy 1
• Do not miss hypoactive delirium – it is commonly underdiagnosed and carries higher mortality than hyperactive forms 4
• Do not defer psychotherapy while waiting for medications to work – psychotherapy is the primary treatment and medications are adjunctive 1, 2, 3
• Do not overlook comorbid depression and anxiety – these conditions are present in the majority of DPD patients and require concurrent treatment 1, 8, 7