Medical Mimics of Psychiatric Conditions, Part 1

Syphilis

Late stages of syphilis can present with a wide variety of psychiatric symptoms, including personality disorder, psychosis, delirium, and dementia. As with HIV, there has been a resurgence of syphilis cases, and screening is now often a routine part of a neuropsychiatric work-up. The EP should consider syphilis in the differential for any new-onset psychiatric complaint.^4,5

Typhoid Fever

Although this severe febrile illness is uncommon in the United States, it is endemic to many tropical countries within Africa, Southeast Asia, and Central and South America. Typhoid is characterized by a stepwise fever that can progress to abdominal distension, toxemia, and potentially bowel perforation. It is also known to present with psychiatric symptoms such as acute confusion, psychosis, generalized anxiety disorder, and, though rare, depressive disorder. Physicians traveling to rural endemic areas should be aware of these neuropsychiatric presentations to avoid misdiagnosis and delay of treatment.⁶ Other infectious endemic diseases with reports of neuropsychiatric components are neurocystercercosis, Lyme disease, and African trypanosomiasis.

Pharmacological Withdrawal Syndromes

Alcohol

Alcohol withdrawal is a common presentation in the ED, and up to 24% of US adults brought to the ED by EMS suffer from alcoholism. Typically characterized by tachycardia, hypertension, and tremors, alcohol withdrawal syndrome can also feature psychiatric components such as agitation, hallucinations, persecutory delusions, and even self-mutilation.⁷ Evidence-based protocols indicate loading doses of benzodiazepines as a mainstay of treatment, with supplemental barbiturates or propofol in cases of treatment failure.⁸

Benzodiazepines

Withdrawal from therapeutic doses of benzodiazepines can potentially cause psychiatric symptoms, including sleep disturbances, irritability, anxiety, panic attacks, tremor, and perceptual changes. Withdrawal from higher doses of benzodiazepines can lead to more serious presentations, such as seizures and acute psychosis.⁹ Withdrawal symptoms can develop from discontinuation of the drug and with non-tapered switching between benzodiazepines.¹⁰

Opiates

Opiate withdrawal is an unpleasant experience characterized by generalized pain, nausea and vomiting, sweating, and tachycardia. Neuropsychiatric complaints such as anxiety, agitation, and irritability can also be present. More severe agitation has been described in naltrexone-accelerated detoxification^.11

Cannabis

Recent literature on cannabis use indicates a high prevalence and clinical significance of associated withdrawal symptoms in frequent users. There appear to be two subsets of cannabis withdrawal—one characterized by weakness and hypersomnia, and the other by anxiety, depression, restlessness, and insomnia.¹²

Estrogen

Withdrawal from endogenous estrogen has been hypothesized as a possible cause of puerperal psychosis.¹³ Estrogen withdrawal outside of this setting, however, can and does occur, and recent literature has shown episodes of reversible psychosis associated with the discontinuation of both oral contraceptive regimens and hormonal therapy for menopausal symptoms.

Acute Metabolic Conditions

Hypoglycemia

Hypoglycemia, most often encountered as a side effect of insulin or oral hypoglycemic therapies, is a potentially lethal cause of confusion, anxiety, nervousness, and seizures. Nocturnal hypoglycemia can manifest as nightmares, crying out, and confusion upon awakening. A fingerstick blood-glucose test is an absolutely vital part of the initial work-up of any patient with an altered mental status or overt psychiatric complaint.¹⁴

Central Pontine Myelinolysis

A potentially devastating neurological condition associated with malnourishment and alcohol dependence, central pontine myelinolysis (CPM) is classically exacerbated by rapid overcorrection of hyponatremia. While the disease can manifest primarily with quadriplegia or pseudobulbar palsy and eventual progress to the dreaded “locked-in” syndrome, early presentations can include psychiatric symptoms such as behavioral changes, psychosis, and cognitive disturbances. Patients with early signs and symptoms of CPM have been misdiagnosed as having schizophrenia with catatonia, leading to delayed treatment and poor outcomes. The EP should remain vigilant when evaluating for this condition and consider a magnetic resonance imaging study in patients with psychiatric symptoms in the setting of fluctuating hyponatremia.¹⁵

Autoimmune Disorders

Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is one of the most common autoimmune disorders, and has a higher incidence in young women. The disease affects multiple organ systems. Though the classic initial presentation of SLE is fever, joint pain, and rash, the associated neuropsychiatric syndromes of this disease are diverse and surprisingly common, and can be the initial manifestation of the disease. Common psychiatric manifestations of SLE include cognitive dysfunction, anxiety, mood disorders such as depression, acute confusion, psychosis, paranoia, and auditory or visual hallucinations.¹⁶

Anti-N-methyl-D-Aspartate Receptor Encephalitis

Initially described as a paraneoplastic effect of ovarian teratomas, anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is actually an autoimmune disorder that can occur even in the absence of a primary tumor. As with SLE, the condition primarily occurs in young women. Antibodies in the cerebrospinal fluid cause prominent psychiatric symptoms such as acute psychosis, delusional thinking, hallucinations, agitation, and confusion. Although the disease can progress to seizures, movement disorders, autonomic dysregulation, and ultimately death, early recognition and treatment can lead to positive outcomes in up to 80% of cases.¹⁷ While the prevalence of anti-NMDAR antibodies in new-onset psychosis remains unclear, recent literature has suggested widespread screening for the disease in all first presentations of psychotic episodes.^18,19