Use of the cholinesterase inhibitor rivastigmine (Exelon; Novartis) does not decrease the duration of delirium in critically ill patients in intensive care units (ICUs) when added to standard treatment with haloperidol, and might increase the risk for death, according to results of a large, placebo-controlled trial published online November 5 in The Lancet.
Objective: In the treatment of schizophrenia, all currently available oral antipsychotics are administered at least once daily, with strict adherence strongly encouraged to minimize risk of relapse. Based on a better understanding of the brain kinetics of antipsychotics, we have proposed a variation of this approach, “extended” dosing, which allows for intermittent but regular dosing.
Method: We carried out a randomized, double-blind, placebo-controlled trial evaluating 35 individuals with DSM-IV–defined schizophrenia who had been stabilized on antipsychotic therapy. Over a 6-month interval, 18 subjects received their medication as usual (daily), while 17 received their antipsychotic therapy every second day (extended). Outcome measures included clinical scales to assess symptoms (Brief Psychiatric Rating Scale [the primary outcome measure], Calgary Depression Scale), illness severity (Clinical Global Impressions-Severity of Illness scale), and relapse (ie, rehospitalization) rates. Side effects were also assessed, including movement disorders (Barnes Akathisia Scale, Simpson-Angus Scale, Abnormal Involuntary Movement Scale) and weight. The study was conducted from February 2003 to July 2007.
Results: Individuals in the extended dosing group were not at greater risk of symptom exacerbation, relapse, or rehospitalization; indeed, more rehospitalizations occurred in those receiving regular dosing. At the same time, though, there was no indication that side effects were significantly reduced in the extended dosing group.
Conclusions: These results challenge the long-standing dogma that oral antipsychotics must be administered daily in stabilized patients with schizophrenia. Further studies with larger samples are needed to replicate these findings, as well as to elucidate whether postulated clinical advantages can be established and determined to outweigh potential risks.
Oxytocin is a hormone that has been reported to reduce the severity of schizophrenia when administered intra-nasally. Rubin and colleagues from the University of Illinois at Chicago report that women with schizophrenia showed less severe symptoms on the Positive and Negative Syndrome Scale (PANSS) in the mid-luteal phase compared with the follicular phase. Higher oxytocin levels in both men and women were associated with more prosocial behaviors. This lends credence to the potential usefulness of oxytocin in schizophrenia, which also is being studied in autism. As a researcher, I also think this study points to the possibility that PANSS ratings in clinical trials of antipsychotics should control for the menstrual phase to avoid the confounding effects of a decline in severity of psychosis during the mid-luteal phase irrespective of drug treatment.
Oxytocin is a hormone that has been reported to reduce the severity of schizophrenia when administered intra-nasally. Rubin and colleagues from the University of Illinois at Chicago report that women with schizophrenia showed less severe symptoms on the Positive and Negative Syndrome Scale (PANSS) in the mid-luteal phase compared with the follicular phase. Higher oxytocin levels in both men and women were associated with more prosocial behaviors. This lends credence to the potential usefulness of oxytocin in schizophrenia, which also is being studied in autism. As a researcher, I also think this study points to the possibility that PANSS ratings in clinical trials of antipsychotics should control for the menstrual phase to avoid the confounding effects of a decline in severity of psychosis during the mid-luteal phase irrespective of drug treatment.
Peripheral oxytocin is associated with reduced symptom severity in schizophrenia
Objective: In recent years there has been a greater appreciation of the elevated prevalence of cardiovascular risk factors in the schizophrenia population and the liability some treatments have for their development. These vascular risk factors are in turn important risk factors in the development of dementia and more subtle cognitive impairments. However, their impact on the cognitive functions of patients with schizophrenia remains underexplored. The authors investigated whether vascular risk factors influence the cognitive impairments of schizophrenia and whether their effects on cognition in schizophrenia are different from those observed in nonpsychiatric comparison subjects.
Method: The authors compared 100 patients with schizophrenia and 53 comparison subjects on cognitive test performance in 2x2 matrices composed of individual vascular risk factors and group (schizophrenia patients and comparison subjects).
Results: Hypertension exerted a significant negative effect on immediate delayed and recognition memory in both groups. Patients with schizophrenia and hypertension were adversely affected in recognition memory, whereas comparison subjects were not. A body mass index above 25 was associated with negative effects on delayed memory in both groups, although the association fell short of statistical significance.
Conclusions: Given that patients with schizophrenia have a higher prevalence of vascular risk factors than the general population and are undertreated for them, treatment of these risk factors may significantly improve cognitive outcome in schizophrenia.
We know that sildenafil (Viagra) helps restore erectile functioning, but not many people know that it also has cognitive-enhancing and neuroprotective effects in rodents. A double-blind, placebo-controlled study from Iran by Akhondzadeh et al suggests that sildenafil can significantly improve negative symptoms of schizophrenia. The study may lead to an important adjunctive use of this drug if it is replicated with a larger sample. The putative mechanism is the inhibition of phosphodiesterase 5 (PDE5), resulting in increased cyclic guanosine monophosphate (cGMP), which may correct the hypofunctioning N-methyl-D-aspartic acid (NMDA) glutamate receptor believed to be associated with elevated dopamine in the mesolimbic tract (causing positive symptoms) and a decline in dopamine in the mesocortical tract (causing cognitive deficits and negative symptoms).
Drinking beet juice increases blood flow to the brain in older people, a finding that suggests the dark red vegetable may fight the progression of dementia, a new study shows.
Beet roots contain high concentrations of nitrates, which are converted into nitrites by bacteria in the mouth. And nitrites help open blood vessels in the body, increasing blood flow and oxygen to places lacking in oxygen.
Previous studies have shown that nitrites -- also found in high concentrations in celery, cabbage, and other leafy, green vegetables like spinach -- widen blood vessels, but researchers say this was the first to find that nitrites also increase blood flow to the brain.
Studies comparing antidepressants with benzodiazepines in the treatment of GAD showed that although benzodiazepines work quickly, the antidepressants lower anxiety more effectively in the long term.[11] Antidepressants that have been approved by the United States Food and Drug Administration (FDA) for the treatment of GAD are extended-release venlafaxine,[12] duloxetine,[13] escitalopram,[14] and paroxetine.[15] Although not FDA approved, citalopram has also been found to be effective for the treatment of GAD.[16] Whereas benzodiazepines have been shown effective for shortterm anxiety, they may worsen depression, a common comorbidity of GAD, and cause other cognitive adverse effects such as sedation and anterograde amnesia. Individuals with a history of substance abuse or dependence should not use benzodiazepines, but patients with no such history rarely abuse these agents and can use them safely.[17] Buspirone and pregabalin also have proven efficacy for GAD.[18–21]Adjunctive Use of Atypical Antipsychotics for Treatment-resistant Generalized Anxiety DisorderTable 1. Summary of Clinical Trials of Adjunctive Use of Atypical Antipsychotics for Treatment-Resistant Generalized Anxiety Disordera
Agent Study Design No. of Patients Study Duration (wks) Mean Daily Dose (mg) Change in Assessment Score Mean Weight Gain (lbs)b Aripiprazole[30] Open label 17 4.9 16.9 CGI-S: −1.6 NR Aripiprazole[31] Open label 10 9 NR HAM-A: −20.6 7.1 Aripiprazole[32] Open label 9 6 13.9 HAM-A: −12
CGI-I: 8 of 9 patients rated as much improved or very much improvedNR Aripiprazole[33] Open label 23 8 10.5 HAM-A: −6.7
CGI-S: −12.5 Olanzapine[34] Randomized, controlled 21 6 8.7 HAM-A: olanzapine −7 vs placebo −3.9 (p=0.4)
CGI-S: 67% of patients rated as not at all ill or borderline ill11 Quetiapine[35] Randomized, controlled 58 8 182 HAM-A: quetiapine −12.5 vs placebo −5.9 (p=0.002) 5.2 Quetiapine[36] Randomized, controlled 22 8 120 HAM-A: quetiapine −2.6 vs placebo −0.3 (p=0.98) 2.7 Quetiapine[37] Open label 40 12 386 HAM-A: −20.6 1.1 Risperidone[38] Open label 16 8 1.12 HAM-A: −6.75
CGI-S: −1.533.9 Risperidone[39] Randomized, controlled 40 5 1.1 HAM-A: risperidone −9.8 vs placebo −6.2 (p=0.034) 2.3 Risperidone[40] Randomized, controlled 390 4 0.86 HAM-A: risperidone −9.26 vs placebo −9.12 (p=0.858)
PaRTS-A: risperidone −8.54 vs placebo −7.61 (p=0.265)2.65 Ziprasidone[41] Open label 13 7 40 HAM-A: −11.2 0.2 HAM-A = Hamilton Rating Scale for Anxiety (lower scores indicate less severe symptoms of anxiety); CGI-S = Clinical Global Impressions-Severity (lower scores indicate less severe illness); CGI-I = Clinical Global Impression–Improvement; NR = not reported; PaRTS-A = Patient-Rated TroublingSymptoms for Anxiety.
aAll atypical antipsychotic treatment was added to current antidepressant therapy.
bIn patients who received the atypical antipsychotic.
Atherosclerosis does not appear to increase the risk for incident depression in older adults — a finding that runs contrary to the so-called vascular depression hypothesis, which asserts that vascular factors precede the onset of depression in this patient population.
The US Food and Drug Administration (FDA) has approved dextromethorphan HBr and quinidine sulfate 20 mg/10 mg capsules (Nuedexta; Avanir Pharmaceuticals, Inc) as the first treatment for pseudobulbar affect (PBA).
PBA occurs secondary to brain injury or neurologic conditions such as multiple sclerosis, amyotrophic lateral sclerosis (ALS), and stroke. Also known as emotional incontinence, it is characterized by sudden outbursts of involuntary crying and/or laughing that can cause anxiety and embarrassment in public settings.
Our patient was a 65-year-old right-handed woman. In August 2003, her family noticed her mild memory disturbance, and she developed delusions that someone intruded into her house, always watched her, and stole her bankbook. In March 2005, she developed auditory hallucinations that someone told her bad things. She also insisted that someone let snakes loose in her house and that someone hid himself under the stool and watched her. She was first diagnosed with schizophrenia and prescribed risperidone. At the next visit, the Mini-Mental Status Examination was administered and she scored 21/30. MRI showed mild diffuse brain atrophy, and SPECT showed right-dominant decreased rCBF in the temporoparietal lobe. Considering these results, her diagnosis was changed to early-onset Alzheimer’s disease. Donepezil was prescribed, and her psychoses were improved.
Their article describes robust, clinically relevant, and rapid alleviation of depression symptoms in patients with bipolar disorder that persists far beyond the presence of the drug in the body. Ketamine has a terminal half-life of approximately 3 hours. Yet after 2 days, or 16 half-lives, of ketamine, the effect size of its antidepressant effects was large (0.8). Impressively, at 2 weeks there were still traces of the antidepressant effects of single ketamine dose, associated with an effect size of 0.22.
Affective fluctuations during menstruation have drawn considerable interest from researchers for a long time.1 Data indicates increased frequency of depression associated with menstrual period in adolescence,2 though there is limited information about the differences in the course or symptoms of bipolar disorder associated with menstrual period in adolescents. The question of the direction of mood shifts in the course of bipolar disorder with specific phases of menstrual cycle has been raised, albeit with limited and inconsistent results.3 We present a case of an adolescent female with cyclic affective changes akin to rapid cycling bipolar disorder starting in the premenstrual (luteal) period and subsiding with onset of menstruation, and we try to explore the biological underpinnings of inherent propensity for the development of bipolar disorder using quantitative electroencephalography (qEEG)
There was high spectral power in low frequency (theta band) over the right temporal region which was further corroborated by LORETA and revealed high signal density over the right temporal region for the same frequency band
A review3 presented findings of 24 prospective studies of affective fluctuations during the menstrual cycle. In most cases the authors found that negative moods marked by irritability, restlessness, anxiety, tension, migraine, sleep disturbance, and impaired concentration occurred more often during the premenstrual and menstrual phases than at other times in the cycle. There were only a few cases of positive moods—such as an increased feeling of well-being, elation, pleasantness, and activation—during the follicular and midcycle phases.3 This case presents with positive mood state, though irritability and headache were present as seen in premenstrual syndrome (PMS). This is an atypical presentation of PMS as opposed to the more common occurrence of elated moods during midcycle; in our case it occurred in premenstrual phase.7 It has been reported that whereas menstrual problems appear to occur more frequently in younger than in older women, premenstrual symptoms occur more often in older women. This suggests a relation between age and menstrual symptoms.
The overlap in symptomatology between PMS and cyclothymia, often considered to be a variant of manic-depressive illness, has given rise to therapeutic trials of lithium carbonate in women with PMS, with mixed results.14 Lithium treatment has been beneficial in controlling premenstrual affective changes, and this led us to use the same in our case.
There are some high-content sources of serotonin, melatonin, and tryptophan which can provide the body with these substances. These include plantains, pineapples, bananas, kiwis, plums, and tomatoes for serotonin; white and black mustard, wolfberry seeds, and fenugreek seeds for melatonin; and cottage cheese, soy protein, peanuts, beans, wheat flour, and potatoes for tryptophan
To the Editor: Lithium is used with great success in the treatment and prophylaxis of bipolar disorders, unipolar recurrent depression, and endogenous depression that is resistant to conventional treatment. It is also known to be neurotoxic at higher serum levels. In rare cases patients develop symptoms of intoxication even with normal lithium levels.
Case Report
A 61-year-old man with history of bipolar disorder that was managed with lithium for more than 20 years presented with complaints of psychomotor slowdown, unsteady gait, memory deficits, restlessness, sleep disorder, and severe tremor in his hand that prevented him from eating or drinking properly. These symptoms had begun in the previous week. There was no recent history of fever, respiratory, gastrointestinal, or urinary complaints. He was medicated with lithium, 800 mg/day, and fluvoxamine, 200 mg/day, and the dosage of his medication had remained unchanged over the last year.
Neurological examination showed psychomotor slowdown, inattention, temporal disorientation, severe episodic memory impairment, motor and verbal perseveration, slurred speech, and hypophonia. Symmetrical global and segmental bradykinesia and lead-pipe rigidity, as well as tremor at rest, intention, and posture, were also evident. His gait was abnormal with shuffling small steps and a hunched-forward upper body.
An analytic study revealed no abnormalities, including CBC, renal, thyroid and hepatic function, and PCR. Lithium serum levels were normal (1.0 mmol/liter).
EEG showed diffuse slow background activity, mainly at 5–6 Hz, with periods of greater lentification at 3 Hz, which is compatible with moderate to severe encephalopathy. A brain CT was normal. The patient was admitted and lithium was stopped. There was remarkable clinical improvement over the next days, and he was discharged at day 5, asymptomatic and on valproic acid (300 mg/day).
