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Through its metabolic contribution to glutathione production, cysteine participates in the general antioxidant activities of the body. Through its role as a modulator of the glutamatergic system, cysteine influences the reward-reinforcement pathway. Because of these functions, NAC may exert a therapeutic effect on psychiatric disorders allegedly related to oxidative stress (e.g., schizophrenia, bipolar disorder) as well as psychiatric syndromes characterized by impulsive/compulsive symptoms (e.g., trichotillomania, pathological nail biting, gambling, substance misuse). While the dosages, pharmacological strategies (monotherapy versus augmentation), and long-term risks are not fully evident, NAC appears to be a promising, relatively low-risk intervention.
Getting a Knack for NAC
Participants 178 patients with first episode psychosis who had received at least one year of antipsychotic drug treatment between September 2003 and July 2006 and had no positive symptoms of psychosis.
Interventions Patients received either maintenance treatment with quetiapine (400 mg/day) or placebo and were followed up for the next 12 months or until a relapse occurred.
Main outcome measure Relapse assessed monthly and defined as re-emergence of psychotic symptoms (delusions, conceptual disorganisation, hallucinations, suspiciousness, and unusual thought content) according to predefined thresholds.
Results 178 patients were randomised (89 to quetiapine and 89 to placebo). The Kaplan-Meier estimate of the risk of relapse at 12 months was 41% (95% confidence interval 29% to 53%) for the quetiapine group and 79% (68% to 90%) for the placebo group (P<0.001). Although quetiapine was generally well tolerated, the rate of discontinuation due to adverse or serious adverse events was greater in the quetiapine group (18%; 16/89) than in the placebo group (8%; 7/89) (relative risk 2.29, 95% confidence interval 0.99 to 5.28; χ2=3.20, df=1; P=0.07).
Conclusion In a group of asymptomatic patients with first episode psychosis and at least one year of previous antipsychotic drug treatment, maintenance treatment with quetiapine compared with placebo resulted in a substantially lower rate of relapse during the following year.
Maintenance treatment with quetiapine versus discontinuation after one year of treatment in patients with remitted first episode psychosis: randomised controlled trial
The mechanism of antidepressant action of quetiapine is unclear. However, it has been suggested that its antidepressant activity is mediated by its metabolite N-Desalkylquetiapine, which leads to norepinephrine reuptake transporter inhibition and partial serotonin 1A agonism.4 A speculation may be that slow clearance of the metabolites as an age effect or genetic trait in this case led to very high levels of N-Desalkylquetiapine potentiating quetiapine's antidepressant effect and leading to worsening of mania. Moreover, a positron emission tomography (PET) study using quetiapine 750 mg or 450 mg/day found that there was no D2 receptor occupancy at the low dose of quetiapine, while 5HT2A receptor occupancy was consistently high.5 Despite the normal head CT scan, brain-aging related neurotransmitter changes and therefore different medication effects could be considered. Calabrese et al.1 reported an incidence of treatment-emergent mania 2.2% with 600 mg/day of quetiapine and 3.9% with 300 mg/day of quetiapine. The absence of dopaminergic receptors blockade and the high affinity for serotonergic receptors at lower doses, may explain quetiapine's antidepressant activity and worsening mania in case of slow titration in manic patients. In this case, geriatrician treatment practice of "start low and go slow" raised questions.
Worsening Mania Associated With Slow Increase of Quetiapine Dose
After study procedures were completed, the researchers offered venlafaxine XR for six months to the subjects who had relapsed after being switched from venalfaxine treatment to a placebo. Twenty-seven subjects accepted the offer. Preliminary results indicated that they again improved to the same degree as patients who had been on it for 12 months. “These results surprised us,” Rickels said. “If this finding can be repeated, it would mean that patients who are for at least six months on venlafaxine XR could go off medication until the symptoms return.”
Extended GAD Treatment Keeps Relapse Rates Low
Specifically, taking estrogen around the time of menopause is linked to a lowered risk of dementia for women as they enter old age, but estrogen therapy in late life is associated with a higher risk for dementia, according to a retrospective study led by Dr. Kristine Yaffe, chief of geriatric psychiatry at the San Francisco VA Medical Center.
Age During Estrogen Therapy May Impact Later Dementia
Many see seasonal affective disorder (SAD) as synonymous with winter depression. However, depression is only half of the problem; spring and summer mania tend to be ignored. Beginning with winter depression, core symptoms resemble hibernation. People sleep more, eat more, and are less interested in usual activities. They are not sad in mood, typically, and may be unaware that their slowed down, uninterested behavior reflects a kind of depression.
Moreover, light itself is not the only cause of depression. Light interacts with a person's own sensitivity to depression. Some people, especially those with bipolar disorder or recurrent unipolar depression, are sensitive to changes in light, and will develop winter depression even in areas with reasonable light levels, such as Georgia or Italy. Others are insensitive to light, and will not develop SAD even in areas with low light levels, such as New England or Scandinavia.
This leads to another misconception about SAD. It is a diagnosis of exclusion, and should not be diagnosed in persons with bipolar disorder or recurrent unipolar depression. SAD means someone has only depression in the winter, and almost never has depression any other time of year.
Light entrains our circadian rhythms; it is what keeps us on regular sleep-wake cycles. When sleep is impaired and reduced, an antidepressant effect occurs, and, in sensitive persons, mania materializes. This is what takes place in the spring and summer when light greatly increases. Longer duration of sleep leads to depression in sensitive persons. Circadian cycles appear to be biologically abnormal in people with bipolar disorder and recurrent depression, hence their sensitivity to light. One of the effects of lithium, for instance, is to lengthen circadian cycles, which appear to be abnormally shortened in animal models of mania.
I've developed my own recommendations for both winter depression and summer mania, which one could call "light precautions." They are as follows, briefly.
In winter. Increase your exposure to light as much as possible. Go out for a walk at noon for up to an hour without any sunglasses on; sleep with all the blinds up.
In summer. Reduce your exposure to light as much as possible: Always wear sunglasses; get room-darkening shades; and sleep in as much darkness as possible. (It is key to adjust one's exposure to natural morning sunlight. It is amazing how many people who oversleep never think of pulling up their window shades, and how many people who don't sleep enough don't think about getting room-darkening window shades.)
Light Box Treatment
Light box treatment essentially replaces the sunlight that is missing in wintertime. Most light boxes provide about 10,000 lux of light, and are meant to be used in the mornings, which is when the sun would normally have risen earlier than it does in the depths of winter. Patients should read or eat breakfast while exposed to indirect light from the box at about arm's length for about 30 minutes daily. Just as one does not directly look at the sun, patients should not directly look at light boxes; this causes ocular damage.
The Truth About Seasonal Affective Disorder
Все же в его случае адекватнее говорить не об аутоперсонамнезии, а об аутоперсонагнозии, как синониме семантической агнозии на лица (просоп-агнозии), даже более адекватном, так как речь идет не только о лицах, а о сфере «приватного». Стоит напомнить, что термин «агнозия» был введен Зигмундом Фрейдом (1891), в тот период крупным невропатологом, вместо термина «асимболия», в силу нарушения связи не предмета с его знаком (символом), а знака и смысла. Таким образом, зрительное восприятие сохранено, но смысл предмета непонятен. Отсюда старый термин «душевная слепота». Что касается семантической просопагнозии, то это расстройство не восприятия, и не столько памяти, сколько самосознания.
Случай аутоперсонамнезии. Диагностический разброд – подарок антипсихиатрам
