Joseph W. Iskandar

Bath salts-induced delirium and brief psychotic episode in an otherwise healthy young man.

To the Editor: Poison centers took 2,237 calls through mid-May 2011 regarding toxic products marketed as bath salts. Bath salts contain methylenedioxypyrovalerone (MDPV), a chemical that is not approved for medical use in the United States.1 We are reporting a case to document that delirium and a reversible brief psychotic episode can be induced by easily available bath salts, which are undetected on routine urine or blood drug screen and thus require special attention in public health and law enforcement. Case report. Mr A, a 28-year-old white man, was brought to the emergency department in 2011 for investigation of confusion and an altered level of consciousness after recreational ingestion of bath salts (“Lady Bubbles”). The previous night, he had ingested 750 mg of “Lady Bubbles.” The following day, Mr A was found in a confused and disoriented state with both hands soaked in blood. The patient reportedly cut his wrists with a glass, and a broken window was found near the scene. He was taken to the emergency department, where he displayed a fluctuating level of consciousness; disorientation to name, place, and time; marked loosening of associations; and bizarre, agitated, and disorganized behavior. The patient received 1 dose of ziprasidone 20 mg intramuscularly in the emergency department. Mr A’s vital signs were within normal limits; physical examination was unremarkable except for bilateral superficial lacerations with one 1.5-cm full-thickness laceration on his left forearm and one 3-cm full-thickness laceration on his right forearm. Results of extensive blood work, including complete blood count, electrolytes, and liver and renal function tests, were within normal limits. The urine toxicology screen was negative for cannabis, amphetamines, hallucinogens, benzodiazepines, cocaine, opiates, and 3,4-methylenedioxymethamphetamine. His blood alcohol level was < 0.01%. Computed tomography of the head revealed no abnormalities, and remaining workup of sudden onset of altered mental status showed no abnormal results. Initial psychiatric consultation obtained in the emergency department revealed him to be somnolent, difficult to rouse, uncooperative, and profoundly confused. A diagnosis of hallucinogenic (and possibly bath salts–induced) delirium (DSM-IV criteria) was made. Mr A had no psychiatric history and was physically healthy. There were no difficulties within the family. His biological father suffered from depression and committed suicide when the patient was 8 years old. The patient was unemployed and was living at his mother’s house. He had also ingested 250 mg of “Lady Bubbles” a couple of days prior to this episode that resulted in increased heart rate, elated mood, and increased socialization. He had experimented with cocaine and heroin on approximately 10 occasions in the past and reported subjective effects of euphoria and increased talkativeness lasting for a few hours, but no other sequelae. During the first 24 hours of hospitalization, Mr A’s level of consciousness improved; he became more alert and better oriented to time, place, person, and situation. He continued to endorse symptoms of delusional ideation involving misidentification and command auditory hallucinations asking him to “kill himself.” The patient and his psychiatrist agreed to a short-term trial of perphenazine 4 mg twice a day to target psychotic symptoms and then further evaluation after discontinuation of medication. By the third day of hospitalization, his thought disorder improved, his mood was euthymic, and he consistently denied any command auditory hallucinations or delusional ideation. At the time of discharge, the patient reported passing out after taking bath salts with no recollection of events resulting in hospitalization and during the first 24 hours of hospitalization. He was discharged home to the care of his mother; his physicians believed that his improvement had been significant enough that psychiatric admission was not warranted. Classes of designer drugs like bath salts are intended to have pharmacologic effects similar to those of controlled substances but to be chemically distinct from them, thus avoiding legal control. Bath salts for recreational use are sold at “head shops” and on the Internet with names such as “Zoom” and “White Rush.” These products also have been labeled as “plant food” and “pond water cleaner” and sold in ways to circumvent detection or enforcement. Some products are labeled as “novelty collector’s items,” despite additional, pharmaceutical-like labels that indicate dosage.1 The products are believed to contain MDPV, a chemical that is not approved for medical use in the United States, which is believed to lead to very severe paranoia.1 MDPV is a norepinephrine and dopamine reuptake inhibitor. Bath salts are no longer legal alternatives in the United States, as an at least 1-year-long ban by the Drug Enforcement Administration has gone into effect as of March 1, 2011. Some of the patients presenting to the emergency department with bath salt abuse were found to have mental illness.2 We present a case of reversible brief delirium and psychotic episode following ingestion of bath salts in an otherwise healthy young man. Our case shows dose-dependent effects of MDPV. At lower doses, it causes increased talkativeness and sociability, while at higher doses, it causes a psychotic reaction. Bath salts–related brief psychosis is reversible and can be treated with antipsychotics or benzodiazepines. In conclusion, physicians should be aware of the increasing availability of bath salts in “special” plant food or pond cleaner—an availability about which potential abusers may already know. Bath salt use should be included in the differential diagnosis of conditions with sudden onset of delirium and brief psychotic symptoms in younger individuals experimenting with illicit substances despite negative toxicology screen. An increased incidence of reversible brief psychotic episodes might be induced by easily available bath salts, which are undetected on routine urine or blood drug screen. This phenomenon requires attention from a public health and law enforcement perspective.

Successful Treatment With Hydroxyzine of Acute Exacerbation of Panic Disorder in a Healthy Man: A Case Report

To the Editor: In a given year, approximately 6 million American adults aged 18 years or older have panic disorder.1,2 To the best of our knowledge, this is the first report to document the successful treatment of acute exacerbation of panic disorder with hydroxyzine in a healthy adult. Case report. Mr A, a 25-year-old man with a history of panic disorder, presented in 2010 to the emergency department complaining of chest pain, tachycardia, palpitations, hyperventilation, shortness of breath, sweating, nausea, and vomiting. Moreover, he reported derealization, a sense of doom, and constant fear of having another panic attack. Mr A stated that he had been having panic attacks about 3 or 4 times daily for the previous week. Myocardial infarction was ruled out. Blood workup was inconclusive for any other medical cause. Mr A had been on venlafaxine 75 mg/d orally for the previous 6 months. He had taken paroxetine 40 mg/d orally with no improvement for the 6 months prior to starting venlafaxine. Past medical, surgical, and family histories were not significant for any major illnesses. He was employed and single and smoked half a pack of cigarettes daily, but had no history of alcohol or illegal drug use. The patient denied having any psychosocial stressors. Physical examination findings revealed no abnormalities. Mr A was admitted to the acute psychiatry unit for observation. Upon admission to the unit, hydroxyzine 25 mg 3 times daily was started with no other changes in medication or therapy. The patient received prompt relief, and there were no further panic attacks during his 3-day admission or his 1-month follow-up. To the best of our knowledge, there are no published cases of successful treatment of acute exacerbation of panic disorder with hydroxyzine in healthy adults. There has been clear evidence of the anxiolytic efficacy of hydroxyzine. In a controlled trial in generalized anxiety disorder patients, hydroxyzine demonstrated greater and more rapid cognitive improvement compared to lorazepam.3 Moreover, it has also shown a lack of organ toxicity and an absence of dependency. As reported in our case, an acute exacerbation of panic disorder was effectively managed by hydroxyzine in a healthy adult. If practitioners recognize this association, extensive use of benzodiazepines may be prevented.

Citalopram-Induced Seizures in a Healthy Adult Taking an FDA-Approved Dosage: A Case Report

To the Editor: A retrospective review of published literature disclosed case reports of seizures following citalopram overdose.1 We present a case of citalopram-induced seizures in an otherwise healthy woman taking a US Food and Drug Administration (FDA)–approved dosage. Case report. Ms A, a 50-year-old African American woman, had a past psychiatric history significant for major depressive disorder, no comorbid medical history, and no previously documented seizure disorder. She presented to the emergency department in October 2010 after 2 witnessed generalized tonic-clonic seizures, lasting 2 minutes each, on 2 consecutive days. She was confused upon presentation to the emergency department. Citalopram 20 mg po daily had been started 4 days prior to the first seizure. She had taken sertraline 50 mg po daily for a year, but had stopped taking that drug several years previously after depression did not improve. At the time of presentation, she had been taking gabapentin 300 mg po daily for Mortons neuroma. Past medical and surgical histories were not significant for any major illness. Family history was negative for seizure disorder, stroke, or myocardial infarct. She was an employed single mother of 6 children. She smoked half a pack of cigarettes daily, but there was no history of alcohol or illegal drug use. Physical and neurologic examinations revealed no abnormalities. Ms A was admitted to the general medical floor for observation, which lasted for 4 days. Complete blood cell count, comprehensive metabolic panel findings, thyroid-stimulating hormone level, alcohol level, and urine drug screen findings were within normal limits. Findings of cranial computed tomography and magnetic resonance imaging, with and without contrast, were within normal limits. Electroencephalogram (EEG) also revealed no abnormalities, and no evidence of an epileptic focus was found. Upon Ms As admission to the medical unit, citalopram was stopped; there were no further seizures during her stay in the hospital or in 1 month of follow-up. To the best of our knowledge, there is no published case of seizures associated with short-term use of citalopram within the FDA-approved dosage range of 20 to 40 mg/d2 in healthy adults. We were unable to identify any other cause of the seizures. Prolonged previous uneventful use of sertraline ruled out a general reaction to the selective serotonin reuptake inhibitor (SSRI) class. Citalopram evokes spontaneous EEG spikes in normal rats, and reduces paired-pulse inhibition in both normal and epileptic rats.3 To the best of our knowledge, this is the first report to document that citalopram may induce seizures at low doses, even in a patient who had tolerated another SSRI in the past. If practitioners recognize this association, expensive investigations and extensive hospital stays may be prevented, although prudent practice would very likely still require the type of investigations undertaken with our patient.

A case of intention tremor induced by the combination of aripiprazole and lamotrigine.

To the Editor: In patients with chronic disabling psychiatric conditions in whom many therapeutic interventions have been implemented, augmentation and combination therapies are commonly used to improve the outcome. The number of visits during which a psychotropic medication was prescribed increased from 32.73 million to 45.64 million in less than 10 years in office-based physician practices in the United States.1 Here, we report a case of intention tremor induced by a combination of aripiprazole and lamotrigine. Case report. Ms A was a 60-year-old white woman with a 6-year history of DSM-IV major depressive disorder and generalized anxiety disorder and no history of psychiatric hospitalizations. Her past medical and surgical history was significant for type 2 diabetes mellitus, above-knee amputation, hysterectomy, and arthritis. Her family history was negative for psychiatric disorders. She denied smoking, drinking alcohol, or using illegal drugs. Multiple medications were tried before Ms A became stable on treatment with lamotrigine 300 mg/d for several years. Although the patient was stable, there was room for improvement in her symptoms, and in February 2011, aripiprazole 5 mg/d was added as an augmenting agent. The patients symptoms improved, and she became socially active, volunteering at the local hospital and spending time with her friends. However, 2 months after starting aripiprazole treatment, the patient developed a disabling intention tremor in her hands, head, and jaw. Lamotrigine was tapered off slowly with no deterioration of her mood and complete resolution of her tremor. Moreover, she reported maintaining an active social life at 3-, 6-, and 12-month follow-up. Our patient was prescribed both lamotrigine and aripiprazole for major depression, and she had a therapeutic response, but we noted an interesting adverse effect that can be attributed only to the concomitant prescription of these medications. Aripiprazole, like other atypical antipsychotics, displays antagonistic action at serotonin-2A (5-HT2A) receptors. However, it differs from other antipsychotics in that it is a partial agonist at dopamine-2 receptors and 5-HT1A receptors.2 Both cytochrome P450 (CYP) 3A4 and the polymorphic enzyme CYP2D6 are involved in the metabolism of aripiprazole to its main metabolite dehydroaripiprazole.3 On the other hand, lamotrigine is metabolized predominantly by glucuronic acid conjugation, mainly by UDP-glucuronosyltransferase 1A4 with the inactive 2-N-glucuronide conjugate as the major metabolite.4 Literature suggests that lamotrigine increases the concentration to dose ratios of aripiprazole by 51%.5 According to the Naranjo Adverse Drug Reactions Probability Scale, the intention tremor reaction reported in this case can be classified as a “probable” association between the combination of aripiprazole and lamotrigine and the side effect.6 The onset of the clinical adverse effect is consistent with the administration of the drugs together, and the effect was not present when either drug alone was given to the patient. To our knowledge, this is the first report of a clinical interaction of aripiprazole and lamotrigine that resulted in intention tremor. We anticipate that many more such cases will surface as combination treatment becomes a norm in the treatment of psychiatric illnesses. Clinicians should be vigilant against this problem and should be ready to adjust treatment with discontinuation of either medication if faced with such an adverse effect in their patients.

Panic-attack-induced transient leukocytosis in a healthy male: a case report

The lifetime prevalence of panic attacks is 28.3% in American adults 18 years and older. The age of onset of panic attack extends throughout adulthood; however, it typically develops in early adulthood, with median age of onset of 22 years [Kessler R.C., Chiu W.T., Jin R., Ruscio A.M., Shear K., Walters E.E. The epidemiology of panic attacks, panic disorder, and agoraphobia in the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2006 Apr;63(4):415-24.]. As reported in our case, panic attacks could induce transient leukocytosis in healthy adults. If practitioners recognize this association, expensive investigations and extensive hospital stays may be prevented, although prudent practice would likely still require some type of investigations.

Childhood Trauma and Conversion Disorder in a 16-Year-Old Boy

To the Editor: In the early 1900s, Pierre Janet observed a relationship between conversion disorder and childhood suggesting that dissociation during trauma could be adaptive.1,2 Case report. Mr A, a 16-year-old white boy, was admitted to the hospital after 2 days of episodes of rhythmic jerking of his right upper extremity and generalized tremulous shivering movements. During these episodes, he was unable to speak but was able to follow simple commands. Pediatric neurologic consultation, including sleep-deprived electroencephalograph, ruled out organic cause for the episodes. On day 2 of the hospitalization, he began to complain of urinary retention, as well as penile and groin anesthesia. He required bladder catheterization with normal urine volumes. Psychiatric consultation was requested due to concerns that he might have conversion disorder. History revealed current treatment of attention-deficit/hyperactivity disorder with atomoxetine 80 mg, a recent diagnosis of posttraumatic stress disorder (PTSD), and mild intellectual disability. Mr A had been placed in foster care 2 months prior to admission due to physical and sexual abuse by his father, which had consisted of his father at times standing on Mr A’s penis and striking his penis with a stick as punishment. On the day his seizure-like episodes started, he had been scheduled to meet with the legal team to bring charges against his father. On interview, Mr A reported frequent thoughts of the abuse and worried that he would never be able to have children due to the trauma to his penis. In light of the neurologic symptoms, including nonepileptic seizures, urinary retention, and numbness of his genitalia, Mr A was diagnosed with conversion disorder(DSM-5 criteria). He was provided psychoeducation and supportive therapy by the psychiatric consultant, and his symptoms resolved later that day. At 9-month follow-up, Mr A was in psychotherapy and free of neurologic symptoms. Lifetime prevalence of conversion disorder ranges from 11 to 500 per 100,000 population.3 Risk factors include low socioeconomic and educational status, low psychological sophistication, and rural settings,3 all features of our patient. A review of nonepileptic seizures found nearly one-third of patients reported childhood sexual abuse.4 To our knowledge, 2 similar cases have been published. One was the case of an 11-year-old boy with urinary retention, erectile dysfunction, and penile anesthesia following circumcision, and another was of a 15-year-old girl who was sexually and physically abused by her father and presented with tremor and urinary retention.5,6 Most conversion symptoms resolve before hospital discharge, but as many as 20%–25% relapse within 1 year,7 and 4%–15% are eventually diagnosed with a neurologic disorder.8,9 It was prescient that Janet1 connected childhood trauma to transient neurologic disruptions, such as conversion symptoms. It is likely that Mr A’s recent discussions of his trauma, and court proceedings against his father, exacerbated his PTSD. Physiologically, it is plausible that overwhelming stress could increase sympathetic nervous system tone, causing transient urinary retention. Also, the “emotional numbing” often described in PTSD sufferers, and those who self-mutilate in the context of past abuse, may involve disturbances of endogenous opiates or mechanisms of auto-anesthesia that have evolved to help endure extreme pain or stress. In our case, the transient genital numbing may be a sort of “somatic flashback” to his body’s attempts to numb the pain of physical assaults on his genitals. Our patient’s prognosis is enhanced by a clearly identifiable stressor, an emotionally supportive foster parent, and initiation of trauma-focused cognitive-behavioral therapy for children with PTSD. We should be aware that conduct disorder presents in a range of different motor and sensory deficits, and that some of these symptoms may be directly related to specific traumatic or extremely stressful experiences. Identifying these connections may expedite diagnosis and treatment.