Separation anxiety disorder (SAD) is the most common anxiety disorder of childhood and a frequently missed diagnosis in adults, where it presents as disabling fear of being apart from a spouse, parent, or child. DSM-5-TR moved SAD out of the childhood-onset chapter and into the anxiety disorders, recognizing that the syndrome can begin or persist across the lifespan with a 12-month adult prevalence near 1-2%.¹ The core feature is excessive, developmentally inappropriate distress about separation from major attachment figures, lasting at least four weeks in children and adolescents and six months in adults, with functional impairment.¹ First-line treatment in youth is cognitive behavioral therapy with graded exposure; SSRIs are added for moderate to severe cases or when access to therapy is limited.^2-3 Bottom line: ask about it deliberately — both pediatric and adult patients underreport, and untreated SAD predicts later panic disorder, agoraphobia, and depression.⁴

SAD is common, female-predominant, and often the first anxiety syndrome a child develops. Adult-onset and adult-persistent forms are increasingly recognized and substantially under-diagnosed.

Prevalence

• Lifetime prevalence approximately 4-5% across the population, with the National Comorbidity Survey Replication estimating 4.1% in children and 6.6% in adults across the lifespan.⁵
• 12-month prevalence in children and adolescents around 4%; adult 12-month prevalence approximately 0.9-1.9%.^1,5
• Most common anxiety disorder in children under 12.

Onset and course

• Median age of onset in childhood, often between ages 7 and 9; a second peak occurs in early adulthood.
• Approximately one-third of childhood cases persist into adulthood; conversely, roughly three-quarters of adults with SAD report onset after age 18, making it a true adult-onset disorder for many.⁵
• Symptoms wax and wane with developmental transitions: school entry, parental illness, immigration, and bereavement are classic precipitants.

Sex and demographics

• Female-to-male ratio approximately 2:1 in community samples, narrower in clinical samples.¹
• Higher rates in lower-income households and in children of parents with anxiety or mood disorders.

Comorbidity

• High comorbidity with other anxiety disorders (generalized anxiety, specific phobia, social anxiety), major depressive disorder, and ADHD in youth.
• In adults, strongly associated with panic disorder, agoraphobia, and PTSD; lifetime suicidal ideation is elevated relative to the general population.^4-5

Risk factors

• Behavioral inhibition in temperament; parental anxiety; insecure attachment.
• Stressful life events, especially loss, parental divorce, and major medical illness in a caregiver.
• Female sex and family history of anxiety disorders confer the strongest replicated risk.

SAD sits at the intersection of attachment biology and the broader fear-circuit dysregulation seen across anxiety disorders. No single lesion accounts for the syndrome; instead, converging temperamental, genetic, and environmental factors load onto a developmentally sensitive threat system.

Neurobiology

• Hyperactivity of the amygdala and reduced top-down regulation by the ventromedial prefrontal cortex during cues of separation or social threat, mirroring findings across pediatric anxiety disorders.⁶
• Dysregulation of the hypothalamic-pituitary-adrenal axis with elevated cortisol reactivity to separation paradigms in young children.
• Oxytocinergic and noradrenergic systems are implicated in attachment-related distress, though human evidence remains preliminary.

Genetics

• Heritability estimates from twin studies in the 40-60% range for childhood SAD, with substantial overlap with the broader anxiety and panic phenotype.⁶
• No replicated single-gene findings; polygenic risk for anxiety and neuroticism predicts SAD non-specifically.

Environmental contributions

• Parental overprotection and parental anxiety amplify avoidance and reinforce the child's appraisal of separation as dangerous.
• Insecure-resistant Attachment patterns in infancy predict later anxiety symptoms, though most insecurely attached children do not develop SAD.
• Acute stressors — bereavement, parental hospitalization, school transitions, immigration — frequently mark the onset.

Integrative model

• The dominant developmental model frames SAD as the convergence of an inhibited temperament, a hyper-reactive fear circuit, and an environment that does not adequately support graded autonomy. Avoidance maintains the disorder by preventing corrective learning.

DSM-5-TR places SAD within the anxiety disorders chapter and removed the childhood-onset requirement that anchored DSM-IV. The core threshold is excessive, age-inappropriate fear of separation from attachment figures producing meaningful impairment.¹

Core requirement

• Developmentally inappropriate and excessive fear or anxiety about separation from those to whom the individual is attached, evidenced by at least three of the following:
  • Recurrent excessive distress when anticipating or experiencing separation from home or attachment figures.
  • Persistent worry about losing major attachment figures or harm befalling them (illness, accident, death).
  • Persistent worry that an untoward event will cause separation (getting lost, being kidnapped, becoming ill).
  • Reluctance or refusal to go out, away from home, to school, to work, or elsewhere because of fear of separation.
  • Excessive fear of, or reluctance about, being alone or without attachment figures at home or in other settings.
  • Reluctance or refusal to sleep away from home or to sleep without being near a major attachment figure.
  • Repeated nightmares involving the theme of separation.
  • Repeated complaints of physical symptoms (headaches, stomachaches, nausea, vomiting) when separation occurs or is anticipated.

Duration and impairment

• At least 4 weeks in children and adolescents.
• At least 6 months in adults (this criterion may be applied flexibly given clinical judgment).
• Clinically significant distress or impairment in social, academic, occupational, or other important areas of functioning.¹

Exclusions

• Not better explained by another mental disorder — for example, refusal to leave home in autism spectrum disorder, delusion-driven avoidance in psychotic disorders, fear of being without a trusted companion in agoraphobia, or worry about ill health in illness anxiety disorder.

ICD-11 differences

• ICD-11 (6B05) retains separation anxiety disorder as a single diagnosis applicable across the lifespan and similarly removed the childhood-onset requirement.⁷
• ICD-11 does not specify a minimum number of symptoms; the diagnosis rests on the clinician's judgment of developmentally inappropriate, persistent, impairing separation fear.

Presentation tracks development. A 7-year-old with school refusal and morning stomachaches, a teenager who cannot tolerate a sleepover, and a 35-year-old who cannot bear her husband's business trips share the same underlying anxiety, expressed through age-appropriate channels.

Children

• School refusal is the most common clinical entry point; mornings are worst, with somatic complaints (abdominal pain, headache, nausea) that remit when the child is allowed to stay home.
• Refusal to sleep alone, repeated requests to call or check on parents, and nightmares with themes of harm to caregivers.
• Tantrums, crying, or pleading at the moment of separation; the child may shadow the parent through the house.

Adolescents

• Reluctance to attend overnight trips, camp, or college away from home.
• Frequent texting or calling of parents; somatic complaints replace overt distress.
• Often co-presents with social anxiety and depressive symptoms.

Adults

• Excessive worry about the safety of a spouse, partner, child, or aging parent.
• Difficulty traveling alone, working away from home, or sleeping apart from the attachment figure.
• Repeated phone calls or location-checking; somatic anxiety symptoms during separation.
• Frequently misdiagnosed as panic disorder, generalized anxiety disorder, or dependent personality.⁵

Course markers

• Symptoms wax and wane; transitions (start of school year, deployment of a partner, illness in a parent) are classic exacerbations.
• Untreated SAD in childhood roughly triples the odds of adult panic disorder and agoraphobia.⁴

The differential turns on the content of the fear and the developmental context. SAD is fear of separation specifically; other anxiety disorders share avoidance and somatic distress but differ in trigger and cognitive content.

Other anxiety disorders

• Generalized anxiety disorder: worry is broad (school, finances, world events), not centered on separation.
• Social anxiety disorder: fear is of negative evaluation by peers, not of separation per se. School refusal in social anxiety improves with parent absence; in SAD it worsens.
• Panic disorder and Agoraphobia: fear of having a panic attack or being unable to escape, not fear of separation. Adult SAD frequently coexists with panic, complicating attribution.
• Specific phobia: discrete trigger (animals, blood, heights), not generalized to separation.

Mood and psychotic disorders

• Major depressive disorder: school refusal and clinginess can occur, but anhedonia, sustained low mood, and neurovegetative changes dominate.
• Psychotic disorders: avoidance is delusion-driven (persecution, contamination), not separation-driven.

Neurodevelopmental and behavioral

• Autism spectrum disorder: refusal to leave home reflects routine rigidity and sensory aversion, not attachment-specific fear.
• Oppositional defiant disorder: school refusal is volitional and not accompanied by autonomic distress at separation.
• Reactive attachment disorder: under-engagement with caregivers, not over-engagement.

Trauma- and stressor-related

• PTSD: avoidance is trauma-cue specific; nightmares replay the event rather than themes of caregiver harm.
• Adjustment disorder with anxiety: clear stressor within 3 months, time-limited; subthreshold for SAD.

Medical mimics

• Hyperthyroidism: tachycardia, weight loss, heat intolerance with anxiety symptoms — check TSH.
• Pheochromocytoma (rare): paroxysmal hypertension, headache, sweating.
• Cardiac arrhythmia, asthma, and migraine can produce somatic symptoms attributed to anxiety.
• Substance- or medication-induced anxiety: caffeine, stimulants, bronchodilators, corticosteroids, cannabis withdrawal.

Diagnosis is clinical. Validated rating scales sharpen severity grading and track response, but no scale substitutes for a careful developmental and attachment history.

Interview approach

• Interview parent and child separately when feasible; children often understate fears in front of parents, while parents may understate to avoid blame.
• Map a typical separation: morning routine, school drop-off, bedtime, parental absences. Look for somatic prodromes and reassurance-seeking loops.
• Assess the parent's response to distress — accommodation (sleeping with the child, allowing school avoidance) maintains the disorder.

Mandatory history

• Onset and precipitants (loss, illness, move, trauma).
• School attendance, peer relationships, sleep arrangements, developmental milestones.
• Family history of anxiety, mood, and substance use disorders.
• Trauma screen (abuse, neglect, witnessed violence).
• Suicide risk screen, especially in adolescents and adults.

Validated rating scales

• Screen for Child Anxiety Related Emotional Disorders (SCARED): 41-item child and parent self-report; SAD subscale.⁸
• Spence Children's Anxiety Scale (SCAS): child and parent versions, separation-anxiety subscale.
• Pediatric Anxiety Rating Scale (PARS): clinician-rated, used in landmark RCTs of pediatric anxiety treatment.
• Adult Separation Anxiety Questionnaire (ASA-27): 27-item self-report for adult separation anxiety.⁹
• General anxiety/depression measures (GAD-7, PHQ-9) to capture comorbidity.

Physical exam and laboratory

• Vital signs, thyroid exam, cardiopulmonary exam.
• TSH if any feature suggests hyperthyroidism.
• Urine toxicology if substance use is suspected.
• Routine neuroimaging is NOT indicated for uncomplicated SAD.

First-line treatment is cognitive behavioral therapy with graded exposure; SSRIs are added or substituted for moderate-to-severe symptoms or when therapy is unavailable. The Child/Adolescent Anxiety Multimodal Study (CAMS) established the combination of CBT and sertraline as superior to either alone for pediatric anxiety disorders, including SAD.²

Pharmacotherapy

• Strong evidence supports SSRIs as first-line pharmacotherapy for moderate-to-severe SAD in children, adolescents, and adults.^2-3
  • Fluoxetine, sertraline, fluvoxamine, and escitalopram all show efficacy in pediatric anxiety disorder trials; fluvoxamine and sertraline have the most SAD-specific data.¹⁰
  • Typical pediatric starting doses: sertraline 12.5-25 mg daily, fluoxetine 5-10 mg daily, escitalopram 5 mg daily; titrate every 2-4 weeks based on response and tolerability.
  • Adult dosing follows standard SSRI ranges for anxiety disorders.
• Evidence suggests SNRIs (venlafaxine, duloxetine) are reasonable second-line agents.³
• Benzodiazepines are not recommended for routine treatment in children; in adults they may be used briefly for severe acute distress with caution given dependence and falls risk.
• Tricyclic antidepressants are no longer first-line; older trials of imipramine for school refusal were inconsistent and the cardiac risk profile is unfavorable.

Psychotherapy

• Strong evidence supports CBT with graded exposure as first-line psychotherapy.^2,12
  • Manualized programs include Coping Cat (ages 7-13), the C.A.T. Project (adolescents), and family-based CBT (FBT).
  • Core components: psychoeducation, somatic management (relaxation, breathing), cognitive restructuring, exposure hierarchy, relapse prevention.
• Evidence suggests parent-focused approaches reduce parental accommodation and improve outcomes; SPACE (Supportive Parenting for Anxious Childhood Emotions) targets accommodation directly.¹³
• For school refusal, rapid graded return-to-school with school-clinician collaboration is preferred over prolonged home tutoring.
• Adult SAD: CBT adapted for adults, with attention to relationship dynamics and panic-spectrum comorbidity, has limited but supportive evidence.

Neuromodulation

• No established role. Neuromodulation (rTMS, ECT) is not indicated for primary SAD.

Adjunctive

• Treat comorbid depression, ADHD, and sleep disturbance, each of which can mimic or amplify separation anxiety.
• School-based accommodations (gradual reentry, identified safe staff member) support exposure work.
• Family work to reduce accommodation is essential whenever a parent is part of the maintenance loop.
• Address parental anxiety; treating an anxious parent improves child outcomes independent of child-directed therapy.

Treatment harms cluster around SSRI activation and discontinuation effects in youth, the burden of exposure work for distressed families, and the iatrogenic risk of over-accommodating school avoidance. The evidence base is strongest in school-aged children and weakest in adults, where the disorder was formally recognized only in DSM-5.¹

Common adverse effects

• SSRIs: GI upset, headache, sleep disturbance, behavioral activation in children (irritability, disinhibition, hyperactivity).
• SNRIs: similar SSRI profile plus dose-dependent blood pressure rise.
• CBT: short-term distress during exposure tasks; family conflict if accommodation pulls back too quickly.

Serious or rare adverse effects

• FDA boxed warning for suicidal ideation and behavior on antidepressants in patients under 25.¹¹
• Serotonin syndrome with SSRI/SNRI plus other serotonergic agents (triptans, tramadol, MAOIs, linezolid).
• Discontinuation syndrome with abrupt SSRI/SNRI cessation, more pronounced with paroxetine and venlafaxine.

Monitoring and discontinuation

• Weekly contact during the first 4 weeks of SSRI initiation in patients under 25, then at decreasing intervals.¹¹
• Plan a 6- to 12-month maintenance course after remission before considering taper.
• Taper SSRIs gradually over weeks; counsel families about discontinuation symptoms.

Limitations of the evidence

• Most RCTs lump SAD with other pediatric anxiety disorders; SAD-specific effect sizes are extrapolated.
• Adult SAD trials are sparse; treatment recommendations rely on extrapolation from pediatric data and from related anxiety disorders.
• Long-term (>2 year) follow-up data are limited; relapse rates after treatment discontinuation are not well characterized.
• Underrepresentation of racially, ethnically, and socioeconomically diverse populations in major trials.

Developmental stage drives presentation, treatment selection, and the dose of family involvement. Comorbid medical illness and trauma reshape both the differential and the treatment plan.

Preschool and early school-age

• Some separation anxiety is normative up to roughly age 6; diagnosis requires intensity and impairment beyond developmental expectation.
• Parent-child interaction therapy adaptations and family-based CBT are preferred; medication is reserved for severe, function-limiting cases.

Adolescents

• Symptoms often shift to somatic complaints, school refusal, and reluctance to engage in age-appropriate independence (overnight trips, driving alone, college).
• Screen for comorbid depression and substance use; suicidal ideation requires explicit assessment.

Adults

• Roughly 75% of adult cases are adult-onset.⁵ Ask about checking behavior, work avoidance, and inability to travel apart from a partner.
• High overlap with panic disorder, agoraphobia, and dependent traits; the diagnosis is missed when clinicians anchor on panic features.

Perinatal

• Pregnancy and postpartum can amplify separation fears, especially around the infant; differentiate from postpartum OCD (intrusive thoughts) and postpartum depression.
• SSRI selection in pregnancy follows general perinatal psychiatry principles (sertraline often preferred); discuss risks of untreated anxiety against medication exposure.

Geriatric

• Late-life SAD often centers on a spouse or adult child; bereavement and caregiver illness are common precipitants.
• Differentiate from prolonged grief disorder and from cognitive impairment driving fear of being alone.

Comorbid medical illness

• Children with chronic illness (asthma, diabetes, oncology) and their parents frequently develop separation-related anxiety; integrated psychosocial support reduces incidence.

Cultural considerations

• Norms for sleeping arrangements, parent-child proximity, and adolescent independence vary widely. Diagnose only when distress and impairment exceed culturally expected patterns.

Most childhood cases improve with treatment, but a meaningful minority persist or relapse, and untreated SAD is a robust antecedent of adult panic and depression.

Treatment response

• In CAMS, response rates at 12 weeks were approximately 81% for combination CBT+sertraline, 60% for CBT alone, 55% for sertraline alone, and 24% for placebo.²
• Gains are largely maintained at 24- and 36-week follow-up, though combination treatment retains an advantage.¹⁴

Long-term outcomes

• Approximately one-third of childhood cases persist into adulthood as SAD; many more transition into other anxiety, mood, or somatic disorders.⁵
• Childhood SAD increases risk of adult panic disorder, agoraphobia, and major depressive disorder by roughly 2-3 fold.⁴
• Functional outcomes (school completion, employment, relationship stability) are poorer when SAD persists or coexists with depression.

Mortality

• No direct mortality from SAD itself; suicide risk is elevated in the context of comorbid depression and panic, particularly in adolescents and adults.

SAD rarely requires hospitalization on its own. Safety questions arise when school refusal becomes total, when somatic complaints prompt repeated emergency visits, or when comorbid depression introduces suicide risk.

Hospitalization

• Inpatient admission is reserved for acute suicide risk, severe depression, or medical complications of food/fluid refusal during prolonged separation distress.
• Day-treatment or intensive outpatient programs are useful for entrenched school refusal that has failed outpatient CBT.

Suicide risk markers

• Comorbid major depression, panic disorder, and substance use; family history of suicide; recent loss; access to lethal means.
• Adolescents with school refusal and isolation should be assessed directly; do not assume anxiety alone is benign.

Acute distress management

• For acute panic during forced separation: brief grounding, paced breathing, validation, and resumption of the exposure plan rather than escape.
• Avoid reinforcing avoidance with as-needed benzodiazepines whenever possible.

Adult SAD remains a contested clinical entity in everyday practice, and the optimal sequencing of therapy, medication, and parent work is still being refined.

Adult-onset SAD recognition

• Although DSM-5/DSM-5-TR formally allow adult diagnosis, surveys suggest most adults with SAD are misdiagnosed as panic disorder, agoraphobia, GAD, or dependent personality disorder.⁵
• Whether adult SAD represents a distinct disorder or a dimensional feature of anxiety disorders remains debated.

Treatment sequencing

• Whether to start with CBT alone or combine with SSRI from the outset depends on severity, access to therapy, and family preference; CAMS supports combination for moderate-severe cases but monotherapy may be sufficient for mild presentations.²
• The role of parent-only treatment (e.g. SPACE) versus child-focused CBT is active research; emerging evidence suggests non-inferiority for some families.¹³

Pharmacology gaps

• No medication is FDA-approved specifically for SAD; SSRI use is supported by the broader pediatric anxiety evidence base and by extrapolation in adults.
• Long-term safety of SSRIs in young children is incompletely characterized.

School refusal management

• Disagreement persists about how aggressively to pursue same-day school return versus graduated reentry; rigid policies in either direction underperform individualized plans.

• DSM-5-TR moved separation anxiety disorder out of the childhood-onset chapter and into the anxiety disorders, allowing diagnosis at any age.
• Duration requirement is at least 4 weeks in children and adolescents and at least 6 months in adults.
• The diagnosis requires three or more of eight DSM-5-TR criteria (worry about losing attachment figures, refusal to be alone, refusal to sleep alone, nightmares, somatic complaints, school/work refusal, distress at separation, worry about events causing separation).
• SAD is the most common anxiety disorder in children under 12, with a female-to-male ratio of approximately 2:1.
• Approximately one-third of childhood cases persist into adulthood; the majority of adult cases are adult-onset.
• First-line psychotherapy is CBT with graded exposure; first-line pharmacotherapy is an SSRI.
• The CAMS trial demonstrated combination CBT plus sertraline (~81% response) was superior to either alone for pediatric anxiety disorders.
• All antidepressants carry an FDA boxed warning for suicidal ideation/behavior in patients under 25; weekly monitoring is recommended during initial titration.
• School refusal in SAD worsens with parent absence; in social anxiety disorder it improves with parent absence — a useful bedside discriminator.
• Untreated childhood SAD predicts adult panic disorder, agoraphobia, and major depressive disorder.
• Parental accommodation (sleeping with the child, allowing school avoidance) is a maintaining factor and a treatment target; SPACE explicitly addresses it.
• Benzodiazepines are not recommended for routine treatment of pediatric SAD given dependence risk and paradoxical disinhibition.
• Always check TSH when somatic anxiety is prominent; hyperthyroidism is a classic medical mimic.
• ICD-11 retains separation anxiety disorder (6B05) as a single lifespan diagnosis without a fixed symptom count.

No external funding. No conflicts of interest declared. Peer-review status: pending.