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1.
Psychopharmacol Bull ; 54(1): 33-39, 2024 Mar 04.
Article in English | MEDLINE | ID: mdl-38449474

ABSTRACT

Synthetic cannabinoids (SCs), a class of new psychoactive substances (NPS) commonly known as "spice," has rapidly gained popularity and become the most ubiquitous NPS on the illegitimate drug market. SCs, unlike natural cannabis (NC), are not controlled by international drug conventions, posing a significant risk to public health. These substances are easily accessible, relatively inexpensive, and challenging to detect in routine drug screenings. The existing literature provides strong evidence of an association between NC use and psychosis, but there is significantly less data on SC psychosis. We present a clinical case report of a 51-year-old African American female with no known psychiatric history who was admitted to the inpatient psychiatric unit after reported paranoia and altered mental status for the preceding six days. During hospitalization, she exhibited disorganization, persecutory delusions, extreme agitation, and bizarre behaviors that included the concealment of a set of stolen keys in her vagina, necessitating an ethics consult. After consideration of differentials, the patient was diagnosed with substance-induced psychotic disorder secondary to SC. The patient was stabilized on 3 mg Risperidone at bedtime. After 16-day hospitalization, she reached her baseline and later revealed that she had recently smoked SC for the first time. The primary goal of this case is to highlight the sequelae of SC-associated psychosis. A SC-associated psychosis could drastically vary from NC and is often undetectable on a typical UDS, which may result in a lifelong primary psychotic disorder misdiagnosis.


Subject(s)
Cannabinoids , Psychoses, Substance-Induced , Psychotic Disorders , Female , Humans , Middle Aged , Psychotic Disorders/drug therapy , Delusions , Psychoses, Substance-Induced/etiology , Hospitalization , Cannabinoids/adverse effects
2.
Front Psychiatry ; 14: 1221131, 2023.
Article in English | MEDLINE | ID: mdl-37810598

ABSTRACT

There has been an increase in research on the topic of psychedelic substances and their effects as treatment options in neuropsychiatric conditions. Psilocybin is a psychedelic drug that has recently garnered increased interest as an effective treatment modality for treatment-resistant depression, depression associated with terminal conditions, certain substance use disorders, and obsessive-compulsive disorder. However, sparse data exist as to the effects that psilocybin might have on patients at risk for mania, in large part secondary to the exclusion of this patient population from studies due to the concern for inducing mania or worsening illness course. We describe a case of a 21-year-old male with a recent diagnosis of bipolar II disorder who developed a manic episode following the ingestion of psilocybin in the form of hallucinogenic mushrooms. Given the incidence of depression in those with bipolar disorder, impulsivity, and a tendency to abuse substances associated with the illness, further research is needed into the risks of psilocybin and other psychedelic use in those with bipolar disorder.

3.
Front Psychiatry ; 14: 1103123, 2023.
Article in English | MEDLINE | ID: mdl-36890985

ABSTRACT

Background: Cannabis (Δ9-THC) is the most commonly consumed illicit drug. The Agricultural Improvement Act of 2018 removed hemp, a strain of Cannabis sativa, as a controlled substance. This law allowed the plant to be processed into its components, which contain <0.3% Δ9-THC. As a result, delta-8-tetrahydrocannabinol (Δ8-THC), a federally unregulated substance, grew in popularity in 2020. Δ8-THC is readily available in most gas stations or head shops and may be considered harmless by patients. However, an increasing number of patients admitted for psychiatric hospitalization report use, with limited literature on the effects. Case presentations: This case report describes three individual cases of patients who required admission to a university psychiatric hospital after the regular use solely of Δ8-THC. All three patients developed psychotic and paranoid symptoms concurrently with the use of Δ8-THC, with a severity exceeding their previous historical presentations. The presenting psychotic symptoms were also atypical for all three patients. New-onset violence and visual hallucinations were noted in two of the patients, one patient with no previous psychiatric history and one patient while on a therapeutic dose of his antipsychotic. In the third case, a new onset of bizarre, fixed delusions of puppies dissolving in the bathtub developed. Conclusion: This report adds to the limited body of evidence on Δ8-THC documenting a temporal association between Δ8-THC use and the development of psychotic symptoms. A strong body of research already correlates the continued use of Δ9-THC with psychosis, and Δ8-THC acts at the same CB1 and CB2 receptors as Δ9-THC. Therefore, it is hypothesized that Δ8-THC may have similar adverse psychiatric effects as Δ9-THC. These conclusions are not without speculation, due to the need for self or collateral-reporting of Δ8-THC use as urine drug screening cannot distinguish Δ8-THC from Δ9-THC, and the patients' symptoms could be explained by medication non-adherence and primary psychotic disorders. However, physicians should be encouraged to gather a specific history of Δ8-THC use and treat patients with Δ8-THC-related intoxication and symptoms.

4.
Psychopharmacol Bull ; 51(3): 72-78, 2021 06 01.
Article in English | MEDLINE | ID: mdl-34421146

ABSTRACT

Akathisia is a movement disorder affecting the trunk and limbs, characterized by subjective and objective restlessness. Key signs include continual, repetitive rocking, leg shuffling, and fidgeting. Antipsychotic-induced akathisia is optimally managed by reducing the medication dose or switching to a second generation antipsychotic that is less prone to inducing akathisia. However, since medication changes are often not feasible, we review the available classes of rescue agents for akathisia symptoms. The fitting acronym, "B-CALM", which stands for Beta-blockers, Clonazepam, Anticholinergics, cLonidine and Mirtazapine, will assist prescribers in facile recall of evidence-based treatment options for akathisia. Pharmacological agents such as mianserin, trazodone, Vit B6, amantadine, gabapentin, and pregabalin have also been examined as treatment options for antipsychotic-induced akathisia. Although initial exploratory reports on these agents have been promising, the current evidence is insufficient. Akathisia has a good prognosis when managed early in the course of treatment. A variety of safe rescue agents are available for the management of this condition, however, current evidence best supports the use of propranolol and mirtazapine.


Subject(s)
Akathisia, Drug-Induced , Antipsychotic Agents , Mirtazapine/therapeutic use , Propranolol/therapeutic use , Akathisia, Drug-Induced/drug therapy , Antipsychotic Agents/adverse effects , Humans , Psychomotor Agitation
5.
AACE Clin Case Rep ; 7(3): 189-191, 2021.
Article in English | MEDLINE | ID: mdl-34095485

ABSTRACT

OBJECTIVE: To familiarize the medical community with the less common adverse effects of lithium on parathyroid function, we present a case of lithium-associated hyperparathyroidism followed by the development of new-onset catatonia in a patient with schizoaffective disorder. METHODS: To allow for the safe resumption of lithium, the patient received laboratory screening of serum lithium, blood urea nitrogen, serum creatinine, calcium, and thyroid-stimulating hormone levels. The hypercalcemia was evaluated by measuring parathyroid hormone (PTH), ionized calcium, and 25-hydroxy vitamin D levels. RESULTS: A 58-year-old man with longstanding schizoaffective disorder was admitted for worsening psychotic symptoms following noncompliance with his risperidone and lithium regimen. Exploratory laboratory tests (hospital day 5) showed an elevated PTH level of 72 (reference, 15-65) pg/mL, ionized calcium level of 1.4 (reference, 1.03-1.23) mmol/mL, and a serum calcium level of 11.3 (reference, 8.4-10.5) mg/dL. After the discontinuation of lithium (day 6), anergia (day 7), mutism, and posturing (day 10) developed. Worsening catatonic symptoms of negativism and poor oral intake necessitated dehydration management with intravenous isotonic saline (day 24). The hypercalcemia persisted for 6 weeks. Treatment with cinacalcet (day 43) rapidly normalized the serum calcium levels (day 44). The catatonia, depression, and psychosis began resolving when clozapine (day 50) and electroconvulsive therapy (day 59) were initiated. PTH levels did not normalize until day 82. CONCLUSION: This report describes a case of prolonged hyperparathyroidism and hypercalcemia following treatment with lithium. Catatonia is unusual in patients with lithium-associated hyperparathyroidism but this report suggests that in settings yet to be determined, it is related to hypercalcemia of this syndrome.

6.
Indian J Psychol Med ; 42(5 Suppl): 92S-97S, 2020 Oct.
Article in English | MEDLINE | ID: mdl-33354072

ABSTRACT

Telepsychiatry is a cost-effective alternative to in-person psychiatric consultations. The COVID-19 pandemic brought about a sharp spike in the utilization of telepsychiatry due to ongoing restrictions on gatherings and traveling. In recognition of the importance of telemedicine in general, and telepsychiatry specifically, telemedicine practice guidelines and telepsychiatry operational guidelines have been released. Due to the rising trend in telemedicine, the Insurance Regulatory and Development Authority of India (IRDIA) incorporated teleconsultation health insurance coverage at a level on par with regular in-person consultations. In contrast, in the United States of America, private insurance coverage for telepsychiatry has been in vogue for some time. In this paper we draw comparisons between India and the United States on telepsychiatry and health insurance. We compare the evolving regulatory policies of these two countries in relation to existing insurances plans that are available, the challenges in implementation of new regulations and the possible ways to overcome the challenges to make telepsychiatry affordable to all.

7.
J Am Psychiatr Nurses Assoc ; 24(2): 133-144, 2018.
Article in English | MEDLINE | ID: mdl-29039238

ABSTRACT

BACKGROUND: Impaired sensory gating in patients with acute mental illness predisposes to overstimulation and behavioral dyscontrol. OBJECTIVE: Explore use of sensory reduction interventions on a high-acuity inpatient milieu to reduce high assault/restraint rates. DESIGN: A multidisciplinary team using failure mode and effect analysis to explore high restraint use between 4:00 p.m. and 7:00 p.m. observed patient/staff overstimulation contributed to behavioral escalations. The team implemented sensory reduction/integration improvements over a 5-month period to prevent excessive restraint use. RESULTS: Restraint rates dropped immediately following light and sound reduction interventions and by 72% at 11 months postimplementation. Mann-Whitney statistics for unpaired 6-month comparisons, 1-year pre- and postintervention showed significant reductions: Assault rates (median pre = 1.37, post = 0.18, U = 4, p = .02); Restraint rates (median pre = 0.50, post = 0.06, U = 0, p = .002). CONCLUSION: Sensory reduction during a high-stress time period on a high-acuity psychiatric unit was associated with a reduction in assaults and restraints.


Subject(s)
Inpatients/psychology , Mental Disorders/therapy , Psychiatric Nursing/methods , Quality Improvement , Restraint, Physical/statistics & numerical data , Violence/prevention & control , Adult , Female , Hospitals, Psychiatric , Humans , Inpatients/statistics & numerical data , Male , Physical Stimulation/adverse effects , Violence/psychology , Violence/statistics & numerical data
8.
Article in English | MEDLINE | ID: mdl-29164929

ABSTRACT

In 2013 more than 150,000 Americans died from all types of lung cancer. Small cell lung cancer (SCLC) represents about 13% of all lung cancers and is notoriously associated with paraneoplastic syndromes (PNS). Here we present an interesting case of psychosis associated with one such PNS-- ectopic Cushing syndrome of SCLC. A 56 year old African-American male with no prior psychiatric history who was diagnosed with SCLC two months prior, presented to the ER for treatment of a right arm laceration he sustained while fighting off attackers, with high concern these individuals may have been part of hallucinatory experiences and well-systematized persecutory delusions regarding his wife. Physical assessment was notable for Cushingoid symptoms. Initial results of serum ACTH and cortisol were 221pg/ml (10-50pg/ml) and 37.1 mcg/dl (10-20mcg/dl) respectively. For psychosis, patient was started on Olanzapine which was titrated from 5 to final dose of 10mg nightly. Since patient was not a surgical candidate, he was treated with metyrapone 250 mg BID and radiation therapy was continued throughout hospitalization. Serum Cortisol level decreased steadily after initiation of metyrapone and psychotic symptoms dramatically reduced on olanzapine, metyrapone, and radiation therapy with apparently resolved persecutory delusions at discharge. This case broadens the available literature and provides data on successful symptomatic treatment with olanzapine while biological treatments of the underlying condition were beginning to take effect. As SCLC remains an important cause of morbidity and mortality in the US, it is imperative that physicians be aware of paraneoplastic syndromes and their psychiatric sequelae.

9.
Psychopharmacol Bull ; 47(4): 59-63, 2017 09 15.
Article in English | MEDLINE | ID: mdl-28936010

ABSTRACT

Dextromethorphan (3-methoxy-N-methylmorphinan), also known as "DXM" and "the poor man's PCP," is a synthetically produced drug that is available in more than 140 over-the-counter cough and cold preparations. Dextromethorphan (DXM) has overtaken codeine as the most widely used cough suppressant due to its availability, efficacy, and safety profile at directed doses. However, DXM is subject to abuse. When consumed at inappropriately high doses (over 1500 mg/day), DXM can induce a state of psychosis characterized by Phencyclidine (PCP)-like psychological symptoms, including delusions, hallucinations, and paranoia. We report a noteworthy case of severe dextromethorphan use disorder with dextromethorphan-induced psychotic disorder in a 40-year-old Caucasian female, whose symptoms remitted only following treatment with a combination of an antipsychotic and mood stabilizer. While some states have begun to limit the quantity of DXM sold or restrict sales to individuals over 18-years of age, there is currently no federal ban or restriction on DXM. Abuse of DXM, a readily available and typically inexpensive agent that is not detected on a standard urine drug screen, may be an under-recognized cause of substance-induced psychosis. It is imperative that clinicians are aware of the potential psychiatric sequelae of recreational DXM use.


Subject(s)
Antitussive Agents/adverse effects , Dextromethorphan/adverse effects , Psychoses, Substance-Induced/etiology , Substance-Related Disorders/complications , Adult , Antimanic Agents/administration & dosage , Antipsychotic Agents/administration & dosage , Antitussive Agents/administration & dosage , Dextromethorphan/administration & dosage , Female , Humans , Nonprescription Drugs , Psychoses, Substance-Induced/drug therapy
10.
J Psychiatr Res ; 91: 105-110, 2017 08.
Article in English | MEDLINE | ID: mdl-28327443

ABSTRACT

Attention-deficit/hyperactivity disorder (ADHD) is a common condition with comorbid insomnia reported in >70% of children and adults. These patients demonstrate delays in sleep-wake rhythms, nocturnal rise in melatonin, and early morning rise in cortisol. Given that standard psychopharmacologic treatments for ADHD often do not completely control symptoms in participants with circadian rhythm delay, we sought to test whether bright light therapy (BLT) advances circadian rhythms and further reduces ADHD symptoms over standard treatments. In addition to standard of care, participants with ADHD diagnosis underwent 1 week of baseline assessment followed by 2-weeks of 30-min morning 10,000-lux BLT beginning 3 h after mid-sleep time. Participants minimized overhead light after 4 p.m., wore an actigraphy watch, and recorded BLT time on daily sleep logs. Dim Light Melatonin Onset (DLMO) was assessed at baseline and after 2-week treatment. ADHD symptoms were measured by the ADHD-Rating Scales (ADHD-RS). BLT significantly advanced the phase of DLMO by 31 min [mean time (SEM), 20:36 (0:21) advanced to 20:05 (0:20)] and mid-sleep time by 57 min [4:37 (0:22) advanced to 3:40 (0:16); paired t-tests, p = 0.002 and 0.004, respectively). Phase advances (in DLMO or mid-sleep time) were significantly correlated with decreased ADHD-RS total scores (p = 0.027 and 0.044) and Hyperactive-Impulsive sub-scores (p = 0.014 and 0.013, respectively). Actigraphy analysis for a subset of 8 participants with significant DLMO phase advance revealed no significant changes in total sleep time, sleep efficiency, wake after sleep onset, or percent wake during sleep interval. This is the first successful use of BLT for advancing melatonin phase and improving ADHD symptoms in adults. BLT may be a complementary treatment for both delayed sleep timing and ADHD symptoms in adults.


Subject(s)
Attention Deficit Disorder with Hyperactivity/complications , Attention Deficit Disorder with Hyperactivity/therapy , Circadian Rhythm/physiology , Phototherapy/methods , Actigraphy , Adult , Female , Humans , Male , Middle Aged , Pilot Projects , Predictive Value of Tests , Sleep/physiology , Sleep Initiation and Maintenance Disorders , Young Adult
11.
Psychopharmacol Bull ; 47(1): 8-26, 2017 01 26.
Article in English | MEDLINE | ID: mdl-28138200

ABSTRACT

BACKGROUND: Disasters are mega-scale catastrophic events which cause trauma and mental health sequelae. A review of early pharmacological interventions for the prevention of psychiatric disorders following disasters is sorely needed. METHODS: A literature search of "Psychiatric Sequelae AND Disasters", "Disaster mental health/Disaster psychiatry", "Psychotropics AND Disasters", and "Drug therapy AND Disasters" yielded 213 articles, 38 of which were included in the review. RESULTS: Common post-disaster psychiatric conditions are: posttraumatic stress disorder (PTSD), depressive and anxiety disorders, substance use disorders and medically-unexplained psychological symptoms. Early psychopharmacological interventions to prevent PTSD provide promising evidence for hydrocortisone in medically ill trauma populations. Less robust benefits were noted for other pharmacological interventions. No reported trials have explored prevention of depression or other common post-disaster psychiatric conditions. CONCLUSION: Hydrocortisone shows promise in preventing and reducing the psychiatric sequelae of PTSD following disasters. Further evaluation of hydrocortisone and other potentially beneficial psychopharmacological interventions are needed.


Subject(s)
Disasters , Mental Disorders/etiology , Mental Disorders/prevention & control , Stress Disorders, Post-Traumatic/etiology , Stress Disorders, Post-Traumatic/prevention & control , Anxiety Disorders/drug therapy , Anxiety Disorders/etiology , Anxiety Disorders/prevention & control , Depression/drug therapy , Depression/etiology , Depression/prevention & control , Humans , Hydrocortisone/administration & dosage , Mental Disorders/drug therapy , Mental Disorders/psychology , Mental Health , Stress Disorders, Post-Traumatic/drug therapy , Stress Disorders, Post-Traumatic/psychology , Substance-Related Disorders/drug therapy , Substance-Related Disorders/etiology , Substance-Related Disorders/prevention & control , Survivors/psychology
12.
Psychopharmacol Bull ; 47(1): 40-44, 2017 01 26.
Article in English | MEDLINE | ID: mdl-28138203

ABSTRACT

Valproic acid (VPA) is an FDA-approved medication widely prescribed for seizures, migraines, and mixed or manic episodes in bipolar disorder. Hyperammonemia is a rare complication of VPA use, which can result in high morbidity and occasionally fatal encephalopathy. The scant literature on Valproate Induced Hyperammonemic Encephalopathy (VIHE) is characterized by acute onset of decreasing level of consciousness, drowsiness, lethargy which in rare instances can lead to seizures, stupor, coma, and persistent morbidity and cortical damage. Below we describe a case report of a patient with Bipolar I Disorder with no primary evidence of hepatic dysfunction that was initiated on VPA and olanzapine to address manic and psychotic symptoms. This patient subsequently developed elevated ammonia (NH4) levels that led to a reversible encephalopathy. This cautionary case report highlights the potential for a rare but serious complication from VPA, a medication increasingly used in both neurologic and neuropsychiatric settings. It is imperative that clinicians perform a thorough physical, neurological and diagnostic evaluation, routinely check NH4 and VPA levels when prescribing these agents and exercise caution when VPA is concomitantly prescribed with antipsychotics and cytochrome P450 inducing antiepileptic medications.


Subject(s)
Antimanic Agents/adverse effects , Bipolar Disorder/blood , Brain Diseases/blood , Brain Diseases/chemically induced , Hyperammonemia/chemically induced , Valproic Acid/adverse effects , Bipolar Disorder/drug therapy , Female , Humans , Middle Aged
16.
Chronobiol Int ; 30(4): 598-606, 2013 May.
Article in English | MEDLINE | ID: mdl-23445512

ABSTRACT

Patients with attention-deficit/hyperactivity disorder (ADHD) often exhibit disrupted sleep and circadian rhythms. Determination of whether sleep disturbance and/or circadian disruption are differentially associated with symptom severity is necessary to guide development of future treatment strategies. Therefore, we measured sleep and ADHD symptoms in participants aged 19-65 who met the DSM-IV-TR (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision) criteria for ADHD and insomnia without psychiatric comorbidities by monitoring actigraphy and daily sleep logs for 2 wks, as well as the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), the ADHD Rating Scale (ADHD-RS), and a clinic-designed sleep behavior questionnaire. Principal components analysis identified correlated circadian- and sleep-related variables in all participants with ADHD who completed the study (n = 24). The identified components were entered into a backwards stepwise linear regression analysis, which indicated that delayed sleep timing and increased sleepiness (ESS) (but not sleep duration or sleep efficiency) significantly predicted greater severity of both hyperactive-impulsive and inattentive ADHD symptoms (p < .05 for partial regression coefficients). In addition, combined subtypes had the most impaired age-adjusted sleep quality (PSQI scores; p < .05 compared with healthy controls; n = 13), and 91.7% of them reported going to bed late due to being "not tired/too keyed up to sleep" compared with 57.2% and 50% of inattentive and symptom-controlled participants, respectively (p < .05). In conclusion, the results of this study suggest that ADHD symptom severity correlates with delayed sleep timing and daytime sleepiness, suggesting that treatment interventions aimed at advancing circadian phase may improve daytime sleepiness. In addition, ADHD adults with combined hyperactive-impulsive and inattentive symptoms have decreased sleep quality as well as the delayed sleep timing of predominately inattentive subtypes.


Subject(s)
Attention Deficit Disorder with Hyperactivity/metabolism , Sleep Wake Disorders/metabolism , Sleep/physiology , Adult , Attention Deficit Disorder with Hyperactivity/drug therapy , Central Nervous System Stimulants/therapeutic use , Double-Blind Method , Humans , Indenes/therapeutic use , Sleep Wake Disorders/drug therapy
17.
J Atten Disord ; 17(7): 583-8, 2013 Oct.
Article in English | MEDLINE | ID: mdl-22997357

ABSTRACT

OBJECTIVE: To explore the potential ADHD phenotype of ADHD-without reported insomnia in comparison with controls and their tolerance of stimulants in a cohort rigorously screened for comorbidities. METHOD: Adults meeting Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.; DSM-IV-TR) criteria for ADHD-without insomnia and matched controls were administered a sleep/medication-timing questionnaire and the Pittsburgh Sleep Quality Index. RESULTS: Among 105 participants, ADHD participants scored in the mild insomnia range and showed reduced sleep quality compared with controls, F(3, 101) = 34.9, p < .05, but no delay in bedtime/mid-sleep-time circadian measures. Sleep quality was similar between stimulant, nonstimulant, and unmedicated groups, χ(2) 2 = 0.445, p = .80. However, later timing of stimulant dosing was correlated with later sleep times, p < .01. CONCLUSION: We isolated a potential phenotype of ADHD-without circadian delay in adults who demonstrated insomnia/sleep quality disturbance by sleep instrument, but lacked sleep-timing delay. Nevertheless, sleep delays were associated temporally with late-dosed stimulants in this group.


Subject(s)
Attention Deficit Disorder with Hyperactivity/complications , Sleep Initiation and Maintenance Disorders/complications , Adult , Aged , Attention Deficit Disorder with Hyperactivity/drug therapy , Dextroamphetamine/therapeutic use , Female , Humans , Male , Middle Aged , Phenotype , Sleep Disorders, Circadian Rhythm/complications , Sleep Disorders, Circadian Rhythm/diagnosis , Sleep Disorders, Circadian Rhythm/drug therapy , Sleep Initiation and Maintenance Disorders/drug therapy , Young Adult
18.
Psychopharmacol Bull ; 44(2): 32-53, 2011 May 15.
Article in English | MEDLINE | ID: mdl-27738354

ABSTRACT

OBJECTIVES: This study evaluated the efficacy of ramelteon for insomnia in adult subjects with ADHD. EXPERIMENTAL DESIGN: For this randomized, double-blind, placebo-controlled crossover trial, 8 mg of ramelteon was given nightly, within three hours of bedtime, to ADHD-insomnia subjects confirmed by DSM-IV-TR, ADHD-RS, MINI, and clinical interview. All subjects underwent two weeks each of ramelteon and placebo. Objective sleep measures were obtained by actigraphy. Subjective measures included: the Epworth Sleepiness Scale (ESS) and ADHD-RS. PRINCIPAL OBSERVATIONS: Of 36 subjects entering the study, 58% met criteria for circadian rhythm sleep disorder (CRSD), delayed sleep phase type. During ramelteon period, mid-sleep time, an indicator of circadian phase, occurred significantly earlier, by ~45 minutes compared to placebo period. An association was noted between the magnitude of the sleep phase advance and the timing of ramelteon administration in relationship to sleep start time, but did not reach statistical significance; maximal efficacy was noted 1.5 hours before bedtime. Paradoxically, ramelteon marginally, but significantly increased sleep fragmentation and ESS scores compared to the placebo state. CONCLUSIONS: Ramelteon is efficacious in maintaining an earlier sleep/wake cycle in adults with ADHD and CRSD but can have paradoxical fragmenting effects on sleep and exacerbate daytime sleepiness. In the presence of a circadian rhythm disorder, the usual dosing and timing parameters for ramelteon need to be carefully considered.

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