Low-dose Quetiapine Research Articles

The role of the clinical pharmacist in the management of psychotropic polypharmacy in the treatment of patients with mental retardation and development disabilities

For many individuals with mental impairments/developmental disabilities (MR/DD) that reside in supported living centers, the potential to be placed on a myriad of psychotropic medications to manage both behavioral and neuropsychiatric disturbances exists. There are distinctive obstacles that a clinical pharmacist that works in a facility providing services to individuals with MR/DD can face as it relates the prescribing of psychotropic medications. As a result of the limited data or clinical trials on the use of psychotropic medications in this particular population, problems can be encountered when multiple psychotropic medications are prescribed. Based on the practice parameters for the assessment and treatment of children, adolescents, and adults with MR/DD, or other comorbid mental disorders published by the American Academy for Child and Adolescent Psychiatry, the problems can include irrational prescribing, inappropriate medication for a given diagnosis, or questionable monitoring of adverse effects. 1 The role of the clinical pharmacist in this practice setting can consist of a continuous assessment of the clinical justification and rationale for why psychotropic polypharmacy is warranted. Polypharmacy can be defined in many different ways and may differ based on the patient population being evaluated. 2 According to Fulton and Allen (2005), polypharmacy is defined as the use of medications that are not clinically indicated; and in clinical practice it is the use of more than a certain number of drugs to treat a condition regardless of its appropriateness. 3 Within an assisted living facility, periodic reviews of drug utilization can be associated with funding for the facility so the evaluation of the appropriateness of medication use, including polypharmacy, may need to be performed on a quarterly, biannual, or yearly basis. The co-occurring use of multiple psychoactive medications in a single patient is becoming an increasingly common and current practice in clinical psychiatry which largely based more on experience rather than evidence. 6 Any patient receiving more than one medication from a specific class (e.g. two antidepressants, two antipsychotics), should have regular reassessment to confirm the necessity of the polypharmacy. In general, polypharmacy is considered to a major health issue not only in primary care setting but in other practice setting as it can lead to unnecessary expenses, wasted time, and possibly mismanagement on the part of the attending clinician if the indication for psychotropic polypharmacy is not routinely evaluated. Furthermore, patients with MR/ DD have an increased potential for drug-drug interactions , side effects of psychotropic medications such as extrapyramidal effects from antipsychotic medications and delirium from benzodiazepines, and possibly unrecognized complications.

Donepezil-Induced Mania

Back to table of contents Previous article Next article LettersFull AccessDonepezil-Induced ManiaSarah Wicklund, M.D., and Mark Wright, M.D.Sarah WicklundDepartment of Psychiatry, Medical College of Wisconsin, Milwaukee, WISearch for more papers by this author, M.D., and Mark WrightDepartment of Psychiatry, Medical College of Wisconsin, Milwaukee, WISearch for more papers by this author, M.D.Published Online:1 Jul 2012https://doi.org/10.1176/appi.neuropsych.11070160AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: The central cholinergic system is believed to play a role in mood disorders, with inhibition of cholinergic activity correlating with mania and facilitation with depression.1 In contrast, six cases of mania related to treatment with donepezil, a centrally-acting acetylcholinesterase inhibitor, have been reported in the literature.2–4 We report a woman who developed mania after starting donepezil.“Mrs. W,” a 65-year-old woman with no personal or family history of mental illness, presented with a several day history of insomnia, hyperreligiosity, and agitation. She had a 6- to 12-month history of worsening cognitive dysfunction, personality changes, and functional impairment. Cognitive examination demonstrated recent-memory impairment and executive dysfunction.Laboratory evaluation, including TSH, MMA, cortisol, RPR, HIV, and serum cryptococcal antigen, was unremarkable. An electroencephalogram was normal. CT and MRI of the brain showed left cerebellar encephalomalacia, white-matter microvascular disease, and lacunar disease in the basal ganglia.The mania did not resolve with discontinuation of donepezil and treatment with low dose quetiapine, and the patient was transferred to a psychiatric hospital 6 days after admission. She was started on donepezil 5 mg daily for suspected Alzheimer’s disease 5 days before presentation.The patient had had a cerebellar stroke 8 years earlier and had hypertension, type II diabetes, and hyperlipidemia. She was noncompliant with all medical medications except clopidogrel.On examination, she acknowledged elevated mood and energy levels. Hypergraphia, pressured speech, and spontaneous singing were noted. Thought examination revealed over-inclusiveness, religious preoccupation, and grandiose delusions.The six patients reported previously who developed mania with donepezil ranged in age from 50 to 78. Four were women; five carried diagnoses of dementia; and one had cognitive impairment related to a cerebral aneurysm and repair. Two patients had histories of bipolar I disorder, and two had depression. Four were on other medications that can cause mania (antidepressants, carbidopa/levodopa). Mania developed in most patients within 1 week of donepezil initiation, and resolved in most within 1 week of discontinuation. Our patient resembled previous reported cases wherein she was elderly, had vascular dementia, and developed mania within days of starting donepezil. It is unclear how donepezil may induce mania; one possibility is an increase in acetylcholine leading to changes in norepinephrine, dopamine, serotonin, or other neurotransmitters.5 Our case and those previously reported suggest that donepezil could precipitate mania in the context of cerebrovascular or other brain diseases, mood disorders, and/or treatment with other medications that can cause mania.Department of Psychiatry, Medical College of Wisconsin, Milwaukee, WI The Authors report no conflicting financial relationships.References1 Janowsky DS, el-Yousef MK, Davis JM, et al.: A cholinergic-adrenergic hypothesis of mania and depression. Lancet 1972; 2:632–635Crossref, Medline, Google Scholar2 Benazzi F: Mania associated with donepezil. J Psychiatry Neurosci 1999; 24:468–469Medline, Google Scholar3 Collins C, Copeland B, Croucher M: Bipolar affective disorder, type II, apparently precipitated by donepezil. Int Psychogeriatr 2011; 23:503–504Crossref, Medline, Google Scholar4 Rao V, Ovitt L, Robbins B: Donepezil induced hypomania. J Neuropsychiatry Clin Neurosci 2008; 20:107Link, Google Scholar5 Decker MW, McGaugh JL: The role of interactions between the cholinergic system and other neuromodulatory systems in learning and memory. Synapse 1991; 7:151–168Crossref, Medline, Google Scholar FiguresReferencesCited byDetailsCited byAcetylcholinesterase Inhibitors in the Treatment of Neurodegenerative Diseases and the Role of Acetylcholinesterase in their Pathogenesis27 August 2021 | International Journal of Molecular Sciences, Vol. 22, No. 17Psiquiatría Biológica, Vol. 26, No. 3Case Reports in Psychiatry, Vol. 2018Cholinesterase inhibitors and affective symptomsMiddle East Current Psychiatry, Vol. 24, No. 3Donepezil-associated manic episode with psychotic features: a case report and review of the literatureGeneral Hospital Psychiatry, Vol. 38Compulsive versifying after treatment of transient epileptic amnesia26 August 2014 | Neurocase, Vol. 21, No. 5Academic Radiology, Vol. 22, No. 8Donepezil-Associated Mania in Two Patients Who Were Using Donepezil Without a PrescriptionJournal of Clinical Psychopharmacology, Vol. 34, No. 6Donepezil-Induced Mania3 March 2014 | The Consultant Pharmacist, Vol. 29, No. 3Reactions Weekly, Vol. 1432, No. 1 Volume 24Issue 3 Summer 2012Pages E27-E27 Metrics PDF download History Published online 1 July 2012 Published in print 1 July 2012

Safety of low-dose quetiapine for insomnia

Safety of low-dose quetiapine for insomnia

Safety of Low Doses of Quetiapine When Used for Insomnia

To evaluate the safety of low doses of quetiapine when used for insomnia. A literature search was performed using PubMed and EMBASE (January 1990-November 2011) using the terms quetiapine, insomnia, sleep, low-dose, subtherapeutic, safety, and weight gain. Two prospective trials were identified that evaluated the effect of quetiapine in primary insomnia. In addition, 2 retrospective cohort studies were identified that evaluated the safety of low doses of quetiapine when used for insomnia. Several case reports on adverse effects with low doses of the drug were also included. Quetiapine is commonly used off-label for treatment of insomnia. When used for sleep, doses typically seen are less than the Food and Drug Administration-recommended dosage of 150-800 mg/day; those evaluated in the studies reviewed here were 25-200 mg/day). At recommended doses, atypical antipsychotics such as quetiapine are associated with metabolic adverse events (diabetes, obesity, hyperlipidemia). Adverse effects in the prospective trials were patient-reported and were minor, including drowsiness and dry mouth; however, the trials were limited by their small sample size and short duration. The retrospective cohort studies found that quetiapine was associated with significant increases in weight compared to baseline. Serious adverse events identified from case reports included fatal hepatotoxicity, restless legs syndrome, akathisia, and weight gain. There are potential safety concerns when using low-dose quetiapine for treatment of insomnia. These concerns should be evaluated in further prospective studies. Based on limited data and potential safety concerns, use of low-dose quetiapine for insomnia is not recommended.

A Case of Neuroleptic Malignant Syndrome with Quetiapine from Iran

To report a case of neuroleptic malignant syndrome (NMS) acutely, secondary to low dose quetiapine in a old man. Clinicians should be aware that NMS with single dose of quetiapine is possible.

Management of psychotic symptoms in Parkinson’s disease

SUMMARY Parkinson's disease psychosis is a major problem complicating the drug treatment of the motor symptoms of the disease. It is one of the leading causes for nursing home placement, exceeding that of motor dysfunction, and is also a greater stressor for caregivers than motor dysfunction. While there is no approved treatment for this problem, it is important to first exclude medical contributions, such as occult infections, then to reduce psychoactive medications, including the medications for motor symptoms, followed by use of low-dose quetiapine or clozapine, giving the bulk of the dose at bedtime.

Low-Dose Quetiapine for Adolescents With Autistic Spectrum Disorder and Aggressive Behavior

Atypical antipsychotics may be useful in treating aggression associated with autistic spectrum disorder (ASD). We evaluated the effectiveness of low-dose quetiapine treatment in ASD adolescent patients with aggressive behavior. Eleven adolescent patients (8 boys and 3 girls) diagnosed with ASD, aged 13 to 17 years, were treated with quetiapine in an open-label study over an 8-week period. The severity of ASD, aggressive behavior, and sleep disturbances were assessed using the Clinical Global Impression-Severity (CGI-S), Overt Aggression Scale, and Child Sleep Habits Questionnaire, respectively. Nonsignificant changes were obtained in autistic behavior after quetiapine treatment (CGI-S: 4.0 ± 0.6 vs CGI-S after: 3.1 ± 1.1; 2-tailed paired t = 1.93; df = 10; P = 0.08). Severity of aggressive behavior decreased significantly after quetiapine treatment (Overt Aggression Scale: 2.1 ± 0.94 vs 1.3 ± 0.64, respectively; 2-tailed paired t = 2.37; df =10; P = 0.028). Sleep disturbances improved significantly (Child Sleep Habits Questionnaire: 49.0 ± 12 vs 44.1 ± 9.6; 2-tailed paired t = 2.98; df =10; P = 0.014) and a positive correlation was found between the improvements in aggression and sleep (Spearman correlation: r = 0.43; N = 11; P = 0.013). Quetiapine was well tolerated. Short-term low-dose quetiapine treatment may reduce aggression levels and improve sleep quality in adolescents with ASD.

“Sleep Attacks” in a Patient With Parkinson’s Disease and Subsequent Psychiatric Decompensation

To the Editor: Sleep disorders in neurodegenerative disorders such as Parkinson's disease are underappreciated. Misdiagnosing a parasomnia can contribute to a worsened quality of life and be devastating in a psychiatrically vulnerable population, as illustrated by the following case. Case report. Mr A, a 64-year-old man, was followed up regularly for his obsessive-compulsive disorder, which had originally been diagnosed 30 years earlier and had recently been in remission on treatment with 80 mg of citalopram daily. He had a history of Parkinson's disease treated with deep brain stimulation, liver transplant following cryptogenic liver cirrhosis, and obstructive sleep apnea treated with nasal continuous positive airway pressure (CPAP). In 2010, he reported having “sleep attacks” at increased frequency during the preceding 2 months. Therefore, he was terrified of falling or doing something “bad” during his sleep. He sustained minor injuries and experienced increasing anxiety about how he arrived in strange places and positions prior to waking up, usually on the bathroom floor. These episodes were not witnessed since he lived alone, and, without anyone to account for his activities, he produced rampant guilt-laden obsessive thoughts about his unseen activities. Intrusive thoughts paralyzed Mr A, and he was no longer able to care for himself. He stopped eating and his weight went from 115 to 95 lb. At this point, he no longer wished to live and began having persecutory delusions that involved punishment for his “bad” behavior. After being admitted to the geropsychiatry unit, Mr A adapted well to its monitored environment and the titration of low-dose quetiapine (12.5 mg in the morning and 25 mg in the evening). No sleep attacks were seen. A second sleep study revealed an elevated hypopnea index of 57.7, consistent with his known obstructive sleep apnea. In addition, there was evidence of rapid eye movement (REM) sleep behavior disorder (RBD) given periodic small limb movements during REM sleep. The catatonic state of REM sleep is disrupted in RBD, which allows for patients to act out their REM-induced dream state. The conventional treatment for RBD is high-dose melatonin or clonazepam,1 but this was not started because the patient's sleep attacks, anxiety, and suicidal ideation were treated with proper use of his nasal CPAP. The sleep attacks did not recur, but the patient remained delusional for 6 months. Parkinson's disease is plagued by sleep-related problems. Sleep architecture is usually experienced as light sleep with frequent awakenings. The majority of patients experience greater insomnia, restless legs syndrome, and vivid dreaming than the general population.2 “Sleep attacks” may be associated with narcolepsy, in which an increasing loss of hypocretin cells has been correlated with disease progression in Parkinson's disease.3,4 Additionally, excessive daytime sleepiness correlates with disease severity and in its extreme form can produce sleep attacks.2 Obstructive sleep apnea may not be more common in Parkinson's disease.5 This is a case of severe obstructive sleep apnea mimicking RBD, a phenomenon that has been termed pseudo-RBD.1 A study by Iranzo and Santamaria6 examined 16 patients with REM sleep–enacting behaviors in addition to a mean hypopnea index of 67.5. Video monitoring found that the abnormal sleep behaviors occurred only during apnea-induced arousals (hypnopompic). As in this case, they remitted with treatment of the underlying obstructive sleep apnea.

Guideline, Education, and Peer Comparison to Reduce Prescriptions of Benzodiazepines and Low-Dose Quetiapine in Prison

Benzodiazepines (antianxiety medications) and quetiapine (an antipsychotic medication) are subject to abuse in prison. Quetiapine is also expensive and has serious side effects. The prescription of these medications in prison for anxiety and insomnia is not the preferred choice. In order to reduce these prescriptions, the University of Medicine and Dentistry of New Jersey-University Correctional HealthCare (UCHC), working within the New Jersey Department of Corrections, provided its psychiatrists with a guideline to the treatment of insomnia in prison. The guideline discouraged pharmacological treatment of insomnia. UCHC then anonymously compared the prescribing practices of its psychiatrists to each other, and educated the psychiatrists about the disadvantages of benzodiazepines and low-dose quetiapine in prison. These techniques reduced the numbers of inmates prescribed benzodiazepines by 38% after 20 months and reduced the numbers of inmates prescribed low-dose quetiapine by 59% after 22 months.

Dose-response and comparative efficacy and tolerability of quetiapine across psychiatric disorders

The atypical antipsychotic, quetiapine, is frequently prescribed on-label and off-label for the treatment of a variety of psychiatric disorders. As quetiapine has variable affinity for dozens of receptors, its clinical effects should also show a large variation as a function of dose and diagnostic category. This study attempts to elucidate the dose-response and comparative efficacy and tolerability (metabolic data) of quetiapine across psychiatric disorders. A systematic search was carried out in the electronic databases, PubMed and EMBASE, using the keywords 'quetiapine' and 'placebo'. Both monotherapy and add-on studies were included. A total of 41 studies were identified. In unipolar and bipolar depression, studies consistently found quetiapine to be effective versus placebo, at doses of approximately 150-300 and 300-600 mg per day, respectively. In bipolar mania, they consistently found quetiapine to be effective at doses of approximately 600 mg per day. In acute exacerbation of schizophrenia, the majority of studies found quetiapine to be effective at doses of approximately 600 mg per day; however, a few large studies found no difference versus placebo. In contrast, studies consistently found quetiapine to be more effective than placebo for stable schizophrenia. In obsessive-compulsive disorder, studies did not consistently find quetiapine to be effective at doses of approximately 300 mg per day. However, studies may have underestimated the efficacy of quetiapine for obsessive-compulsive disorder due to concomitant administration of antidepressants and the utilization of treatment-refractory patients. In generalized anxiety disorder, studies consistently found quetiapine to be effective at doses of approximately 150 mg per day. Finally, analysis of metabolic tolerability data suggests that even low doses of quetiapine may lead to increase in weight and triglycerides across psychiatric disorders. Interestingly, however, quetiapine-induced elevations in low-density lipoprotein and total cholesterol seem to be restricted to schizophrenia patients.

Hyperglycemic Hyperosmolar State Associated with Low-Dose Quetiapine Treatment in a Patient with Bipolar Disorder

There is increasing concern about the development of diabetes mellitus and associated complications in patients administrating second-generation antipsychotics. Previous reports indicate that the risk of quetiapine, although relatively lower, is not negligible. We report a patient with bipolar disorder who, after treating with low-dose quetiapine, develops newly-onset diabetes and hyperglycemic hyperosmolar state. Clinical manifestations and managements of quetiapine-associated diabetes are addressed, and we recommend routine monitoring of serum glucose after initiating quetiapine treatment at any given dose.

P02-250 - Dementia in Parkinson's disease: Case report

IntroductionParkinson's disease (PD) dementia is a rapidly growing global health problem. Dementia in PD is often accompanied with neuropsychiatric manifestations, such as depression, insomnia, visual hallucinations and psychomotor agitation, which need psychiatric attention.ObjectivesThe authors’ aim is to report a case of a 76-year-old female suffering from PD who was admitted to the psychiatric yard exhibiting neuropsychiatric symptoms. A literature's review about PD dementia was also made.Case reportPatient had one psychiatric hospitalization at age 41, due to depressive symptoms. PD diagnose was made at age 65 and initially responded well to levodopa. Over the subsequent years, motor fluctuations and dyskinesias as well as autonomic, cognitive and psychological symptoms gradually developed. At 75 years, patient's family stated that she had been more forgetful, impulsive, showing signs of anxiety and dysphoria. She was hospitalized exhibiting psychomotor agitation, disorientation, insomnia and mainly nocturnal visual hallucinations with persons. Diagnostic testing included: cranial tomography which showed mild generalized atrophy but no other structural cause of her symptoms; laboratory tests with B12, folic acid, thyroid function; syphilis detection test and examinations of serum and urine were normal. The MMSE scored 19. Attention deficits and constructional apraxia were present in clock drawing test. Treatment was initiated with memantine and a low dose of quetiapine. She was discharged after 20 days with improvement of neuropsychiatric symptoms.ConclusionsEarly diagnosis and treatment of dementia in PD may prevent psychiatric hospitalization and avoid patient's and family's distress.

Fatal Hepatotoxicity in an Elderly Patient Receiving Low-Dose Quetiapine

Back to table of contents Previous article Next article Communications and UpdatesFull AccessFatal Hepatotoxicity in an Elderly Patient Receiving Low-Dose QuetiapineMehmet Ilkin Naharci, M.D., Nuri Karadurmus, M.D., Orhan Demir, M.D., Ergun Bozoglu, M.D., Mehmet Ak, M.D., and Huseyin Doruk, M.D.Mehmet Ilkin NaharciAnkara, TurkeySearch for more papers by this author, M.D., Nuri KaradurmusAnkara, TurkeySearch for more papers by this author, M.D., Orhan DemirAnkara, TurkeySearch for more papers by this author, M.D., Ergun BozogluAnkara, TurkeySearch for more papers by this author, M.D., Mehmet AkAnkara, TurkeySearch for more papers by this author, M.D., and Huseyin DorukAnkara, TurkeySearch for more papers by this author, M.D.Published Online:1 Feb 2011https://doi.org/10.1176/appi.ajp.2010.10091292AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: Quetiapine-related liver abnormalities are extremely rare occurrences. We report on a case of fatal hepatotoxicity caused by the lowest dose of quetiapine in an elderly patient.“Ms. B” was a 77-year-old, fragile woman who was brought to the outpatient service of the geriatric clinic with symptoms of increasing fatigue, vomiting, and loss of appetite for 1 week. The patient had recently received treatment with low-dose quetiapine (12.5 mg twice daily) for 9 days, as prescribed by her psychiatrist, for symptoms of agitation and severe insomnia. She had no family or personal history of liver disease or abnormal liver biochemistry, and results of her liver function tests, conducted in our hospital 3 weeks prior, revealed aminotransferase levels within normal limits. The patient gave no history of alcohol use, substance abuse, or smoking, and she was not receiving any medication other than quetiapine.On examination, she was afebrile, with a temperature of 36.8°C. She had a blood pressure measurement of 94/62 mm Hg, a heart rate of 112 beats/minute, a respiratory rate of 28 breaths/minute, and an oxygen saturation rate of 96% on a 2-liter nasal cannula. The patient was not alert, and she was disoriented. Her physical examination was unremarkable otherwise. However, laboratory findings were as follows: leukocyte count, 10.300 mm3; hemoglobin level, 12.1 g/dl; hematocrit level, 37.4%; platelet count, 256.000/mm3; erythrocyte sedimentation rate, 24 mm/h; C-reactive protein level, 3 μg/dl; serum creatinine concentration, 1.43 mg/dl; blood urea nitrogen concentration, 44.63 mmol/l; sodium level, 135.1 mmol/l; potassium level, 5.14 mmol/l; aspartate aminotransferase concentration, 1,415 U/l; (reference range: 10–35 U/l); alanine aminotransferase concentration, 1,565 U/l (range: 10–35 U/l); alkaline phosphatase level, 178 U/l (range: 38–155 U/l); gamma-glutamyl transferase level, 95 U/l (range: 7–32 U/l); total bilirubin, 4.77 mg/dl; direct bilirubin, 3.38 mg/dl; albumin concentration, 3.32; prothrombin time, 56.6 seconds; international normalized ratio, 4.12; and ammonia concentration, 104 g/dl. A diagnostic evaluation for viral, autoimmune, and metabolic diseases was negative, and an abdominal ultrasound using Doppler was not remarkable.Following this extensive work-up, the patient's acute hepatic failure was attributed to an idiosyncratic reaction to low-dose quetiapine. Therefore, quetiapine was discontinued. Although her liver function improved in the following 7 days (aspartate transaminase concentration: 942 U/l, alanine transaminase concentration: 1,020 U/l), her condition continued to deteriorate significantly despite full supportive care in the intensive care unit. “Ms. B” died on the eighth day of her stay in the intensive care unit because of overwhelming multiorgan system failure.The causal relationship between quetiapine and hepatotoxicity was evaluated using Naranjo criteria (1) (see the data supplement accompanying the online version of this case report). The adverse drug reaction was rated as probable. Two cases of quetiapine-related liver abnormalities have been previously reported (2, 3). In the first case, a 58-year old woman had elevated levels of liver function 1 month after initiation of quetiapine (100 mg/day) for treatment of bipolar disorder (2). In the second report, a 21-year-old man received quetiapine (300 mg/day) for irritability and sleep problems. Three days into the patient's treatment, laboratory tests revealed abnormal hepatic enzyme levels (3). Our patient differed from the patients in these prior cases in two notable ways. First, our patient was elderly, unlike the other two patients. Second, she had drastic increases in hepatic enzyme levels while receiving lower doses of quetiapine than the patients in the prior cases.This is the first report, to our knowledge, of fatal hepatotoxicity caused by the lowest dose of quetiapine. For this reason, our opinion is that a dose-independent manner of mechanism, as seen in idiosyncratic reactions, might be the cause. Quetiapine must be administered with care, and liver function should be monitored closely, particularly in elderly or fragile patients treated with the drug.Ankara, TurkeyThe authors report no financial relationships with commercial interests.The patient in this report underwent follow-up evaluation at Gulhane Medical School, Department of Internal Medicine, and Division of Geriatrics, Ankara, Turkey.accepted for publication in November 2010.

Worsening Mania Associated With Slow Increase of Quetiapine Dose

Worsening Mania Associated With Slow Increase of Quetiapine Dose

Sustained Hypotension With Initial Low Dose of Quetiapine in a Middle-Aged Man Receiving an Antihypertensive Agent

To the Editor: Quetiapine may induce orthostatic hypotension associated with dizziness, tachycardia, and, in some patients, syncope especially during the initial dose titration period.1 Sustained hypotension (defined as a systolic blood pressure 60 minutes) with quetiapine has been described only in significant overdoses.2–4 Due to its potential for inducing hypotension, quetiapine may enhance the effects of certain antihypertensive medications.1 We present a case of sustained hypotension in a middle-aged man on an antihypertensive agent with a single low dose of quetiapine. Case report. Mr A, a 46-year-old man, presented in 2010 with the police following self-inflicted lacerations to his wrists and a polypharmacy overdose of acetaminophen, codeine phosphate, and paroxetine in the context of marital discord. He described depressive symptoms, episodic severe anxiety symptoms, and a passive wish to die over the preceding 2 weeks. He had a history of hypertension (controlled well on irbesartan 300 mg/d and hydrochlorothiazide 12.5 mg/d combination; blood pressure at presentation was 139/94 mm Hg). On examination, he presented as markedly distressed, crying, preoccupied with current stressors, and expressing ideas of hopelessness and suicidal ideas with intent. There was a mild derangement of his renal and liver functions, attributable to the overdose, that did not require medical intervention. He was diagnosed with an adjustment disorder with depressed mood (DSM-IV criteria), and the treatment prescribed was escitalopram 10 mg in the morning and quetiapine 50 mg bid for agitation. His antihypertensive medication was unchanged. On the morning that this treatment was initiated, he had a fall 40 minutes after he received his first dose of escitalopram and quetiapine. He had taken his antihypertensive medication as usual that morning, and his blood pressure was within normal limits. On examination at the time of the fall, blood pressure was recorded as 65/43 mm Hg, and his electrocardiogram revealed no abnormalities. There was no loss of consciousness, and he had a full recollection of events afterward. Findings of the rest of the examination were completely within normal limits. Over the next 8 hours, he received intensive medical care, intravenous fluids, gelofusine, and metaraminol 0.5 mg. At the end of 1 hour of this treatment, his systolic blood pressure was 55 mg Hg, and at the end of 8 hours, he achieved a blood pressure of 105/70 mm Hg. Over the next 16 hours, his blood pressure continued to remain unstable, finally stabilizing about 24 hours after the fall at about 120/76 mm Hg. Both the antihypertensive medication and quetiapine were stopped. He maintained his improvement and was discharged from the hospital 10 days later. The patient was being treated with an angiotensin II receptor antagonist and thiazide diuretic for hypertension. Irbesartan blocks the potent vasoconstrictor and aldosterone-secreting effects of angiotensin II, and hydrochlorothiazide has diuretic, natriuretic, and antihypertensive effects.1 This combination is known to potentiate the antihypertensive actions of ganglionic or peripheral adrenergic-blocking drugs, like quetiapine, which has high antagonistic activity at α-adrenergic receptors.1 No other risk factors for hypotension were operative in this case. It is noteworthy that the hypotension was severe and sustained given that the patient had received only his first dose of 50 mg quetiapine and that, prior to receiving this dose, his blood pressure was normal and stable. This suggests caution when initiating the use of quetiapine in individuals receiving antihypertensive medication(s), even in the absence of cardiovascular or other risk factors for hypotension. In such circumstances, we suggest initiation of quetiapine therapy at a dose of 12.5 or 25 mg, slow upward titration, and careful monitoring of blood pressure. This caution is all the more important as quetiapine is increasingly being used for indications other than psychosis, in a variety of treatment settings.5

The acute and chronic effects of combined antipsychotic–mood stabilizing treatment on the expression of cortical and striatal postsynaptic density genes

The detection of changes in postsynaptic gene expression after the administration of mood stabilizers, alone or in combination with antipsychotics, and antidepressants in animal models of drug treatment, may represent a valuable strategy to explore the molecular targets of the mainstay treatments for bipolar disorder. In this study we investigated, in both acute and chronic paradigms, the expression of specific postsynaptic density genes (Homer1a, Homer1b/c, and PSD95) and genes putatively implicated in mood stabilizers mechanism of action (GSK3b, ERK) after administration of first (haloperidol) or second generation antipsychotics (quetiapine 30mg/kg), alone or in combination with valproate. Moreover, we compared the effects of an antidepressant agent widely used in bipolar depression (citalopram) with a low dose of quetiapine (15mg/kg), which has been demonstrated to display antidepressant action in bipolar depression.In striatal regions, Homer1a expression was strongly induced by haloperidol compared to all the other treatments. Haloperidol plus valproate also markedly induced Homer1a, but to a significant lesser extent than haloperidol alone. Also in the chronic paradigm haloperidol, but not haloperidol plus valproate, induced Homer1a expression in all the subregions of the caudate-putamen and in the nucleus accumbens core. The high dose of quetiapine significantly induced Homer1a in anterior cingulated, premotor and motor subregions of the cortex, and the extent of induction was significantly higher as compared to the lower dose. Oppositely, Homer1a expression was decreased in the cortex by citalopram acute administration.ERK gene was upregulated in cortex and striatum by the acute treatment with valproate and with the combination of haloperidol or quetiapine plus valproate, whereas no significant differences were noticed in GSK3b expression among treatments. PSD95 showed a significant upregulation by acute citalopram and by haloperidol plus valproate in both cortical and subcortical regions. Haloperidol and quetiapine 30mg/kg, oppositely, significantly reduced the expression of the gene in the cortex.In conclusion, these results suggest that the combined treatment with a typical or an atypical antipsychotic plus valproate may induce differential modulation of postsynaptic genes expression when compared to the effects of these drugs individually administered.

Quetiapine in the treatment of psychosis in Parkinson’s disease

Psychosis (delusions and/or hallucinations) is a common nonmotor feature of Parkinson's disease (PD). Use of the older 'typical' antipsychotic drugs led to worsening of motor symptoms. The introduction of 'atypical' antipsychotics opened up a range of therapeutic options. These agents include clozapine, risperidone, olanzapine, aripiprazole and quetiapine. All have been used to treat psychosis in PD with varying success. Clozapine is the only drug with proven efficacy. We review the evidence for the efficacy of quetiapine. Eight open-label studies have assessed quetiapine use in 191 patients, with improvement in psychosis recorded in 152 (80%). In addition to the open-label studies, there have been two single-blind, randomized trials comparing quetiapine and clozapine. These studies suggest that quetiapine has similar efficacy to clozapine in controlling psychosis. Following the promising results of the open-label and clozapine comparison studies, five randomized, controlled trials (RCTs) have been performed to further establish the efficacy of quetiapine. Unfortunately, the results have been disappointing. The only positive placebo-controlled study excluded patients with delusions, which seem to be harder to treat than hallucinations. The four negative RCTs discussed seriously undermine the evidence from the open-label studies. The differences in design and interpretation of the RCTs emphasizes the need for further large, well-controlled trials, using strict inclusion criteria, appropriate psychosis rating scales, carer input and clinical significance. Currently, many physicians continue to cautiously offer a trial of low-dose quetiapine empirically. Clozapine should be considered in patients who can tolerate the required blood monitoring.

Statistically Significant Increase in Weight Caused by Low‐Dose Quetiapine

To determine if preliminary data suggest that low-dose quetiapine is associated with weight gain. Retrospective medical record review. Two military hospitals serving active-duty soldiers, family members of service members, and military retirees. Five hundred thirty-four adult military health care beneficiaries who received quetiapine at a total daily dose of 100 mg or less for a minimum of 1 month between January 1, 2005, and June 30, 2008. The mean weight at baseline was 175.68 lbs. The mean ± standard error weight gain compared with baseline was 0.49 ± 0.51 lbs (p=0.335) at 1 month, increasing in a generally linear fashion to 5.56 ± 1.25 lbs (p<0.001) at 6 months, and 10.58 ± 2.20 lbs (p<0.001) at 12 months. Low-dose quetiapine caused a statistically significant weight gain in our study population. This finding highlights the need for greater recognition of the potential for quetiapine to cause undesirable effects, and demonstrates the importance of close monitoring of physiologic parameters during treatment.

Differential pharmacological responses of catatonia-like signs in frontotemporal dementia

Sequential therapeutic trials for catatonoid frontal signs in clinically-evident frontotemporal dementia (n = 2) revealed differential benefits for lorazepam, amantadine, memantine, pramipexole, aripiprazole, quetiapine, citalopram, and donepezil, although certain signs also worsened. Citalopram and donepezil were poorly tolerated. Ramelteon was without effect. While memantine appeared to improve cognition in case 1, this remains to be established by more reliable neuropsychological testing. Parkinsonism (case 2) responded to pramipexole, but not amantadine or levodopa. Possible relationships of catatonoid signs requiring future confirmation include insufficient GABA-A (multiple signs) and D2 (mutism) and excessive NMDA (immobility, rigidity), D2/D3 (mannerisms, verbal perseveration), and 5HT1a (staring) receptor stimulation. Low-dose lorazepam and quetiapine required close monitoring.

Low-Dose Trazodone-Related Drug Eruption

Back to table of contents Previous article Next article LETTERFull AccessLow-Dose Trazodone-Related Drug EruptionPang-Yen Liu M.D.,Nian-Sheng Tzeng M.D.,Pang-Yen Liu M.D.Search for more papers by this author,Nian-Sheng Tzeng M.D.Search for more papers by this author,Published Online:1 Jul 2010https://doi.org/10.1176/jnp.2010.22.3.352.e29AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: Trazodone is a triazole pyridine derivative antidepressant that was first marketed in the United States in March 1982. Structurally, it is unrelated to tricyclic or tetracyclic antidepressants or to monoamine oxidase inhibitors. Because of its favorable anticholinergic and cardiac side effects, it has always been a popular antidepressant with standard dosages ranging from 250 mg to 600 mg daily. It is also a first-line agent for the treatment of insomnia, with typical initial dosage ranges from 25 mg to 100 mg daily. 1 We report a patient with a rare dermatologic reaction to low-dose trazodone. Case ReportA 26-year-old man developed depressed mood, insomnia, poor appetite with weight loss, psychomotor retardation, and suicidal ideation after enlistment in late September 2008. He had no previous personal or family history of psychiatric disorders. His medical history and physical examination were also unremarkable. He had his first depressive episode in May 2007, and then this episode remitted spontaneously 5 months later. The patient was admitted to a psychiatric inpatient ward on October 10, 2008, with an initial diagnosis of recurrent major depressive disorder. On the second day in the hospital, the patient was given the following agents nightly: sertraline, 50 mg; zolpidem, 10 mg; and alprazolam, 0.5 mg. After 10 days in the hospital, his mood improved rapidly. However, his insomnia persisted, and he responded poorly to nightly doses of clonazepam, 4 mg; flurazepam, 30 mg; and low-dose quetiapine, 25 mg. A low dose of trazodone (50 mg at night time) was started on hospital day 19, and then insomnia improved. However, on hospital day 20 he reported an itchy red rash over his anterior chest. On hospital day 21, the rash had become full blown and covered his entire trunk, presternum and back with morbilliform erythematous macules and papules ( Figure 1 ). After a dermatologic consultation, the trazodone was discontinued and an antihistamine was begun. On hospital day 22, no new lesions were noted. By day 24, the maculopapular rash had resolved. FIGURE 1. Skin Rash After Trazodone UseOn the third day of taking trazodone, 50 mg daily, the patient developed typical morbilliform erythematous macules and papules over the presternal region (A) and on his back (B).Discussion A review of the literature for the period between 1984 and 1986 revealed a total of four cases of dermatologic reactions following use of trazodone. Two cases involved dermatologic eruptions when trazodone was given in daily dosages of 200 mg and 25–50 mg, respectively. 2 , 3 One case of erythema multiforme 4 occurred at a daily dosage of 400 mg, and one case of leukocytoclastic vasculitis 5 was reported at a daily dosage of 350 mg. These dermatologic reactions secondary to trazodone occurred mainly within the regular dosage range given for depression. In our case, the dermatologic reactions occurred after the patient received a much lower dose of trazodone, for alleviating sleep disturbances, and the lesions localized on the presternal region and back. Because of safety issues, we did not use a rechallenge, but the clinical picture and the fact that the lesions resolved after trazodone was discontinued suggest the reaction was a low-dose trazodone-induced eruption. In addition, there have been no more reports about trazodone-related drug eruptions during the past 20 years. Our experience was a reminder that the common use of trazodone to treat insomnia, even at a low dosage, may lead to drug reactions.Department of Internal Medicine, Tri-Service General Hospital, TaiwanDepartment of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan