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Re: Klonopin memory claims

Posted by Kon on January 6, 2004, at 20:30:38

In reply to Klonopin memory claims, posted by ian24 on January 6, 2004, at 18:28:41

The balance of studies suggest that long-term benzo use (including klonopin) may cause some memory and cognitive problems in some subjects. I've posted a few of those studies below. There are many more such studies. I've also posted one recent (2003)study that showed no deficits in memory with long-term benzo use (see last study).

Even with risk of cognitive/memory side-effects, this does not mean that benzos are a poor drug choice. In fact, a strong argument can be given that the alternatives (i.e. SSRIs, MAOIs) may have a worse safety profile. Personally, I chose clonazepam (klonopin) because I still believe that benzos overall are a safer drug choice than some of the alternatives.

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Pharm Des. 2002;8(1):45-58.

Cognitive and sedative effects of benzodiazepine use.

Buffett-Jerrott SE, Stewart SH.

Department of Psychology, Dalhousie University, Life Sciences Center, 1355 Oxford Street, Halifax, Nova Scotia, Canada B3H 4J1. sjerrott@is2.dal.ca

This paper reviews the effects of benzodiazepines (BZs) on the performance of tasks measuring human cognitive abilities. The paper reviews the most common cognitive side effects of BZs: increased sedation, decreased attention, and anterograde amnesia. In particular, this paper focuses on recent findings regarding time course-related effects on BZ-induced deficits in explicit and implicit human memory performance. Specifically, we reviewed recent research indicating that both explicit memory and priming are impaired by BZs if the encoding task takes place near the time of the theoretical peak plasma concentrations of the drug. Although BZs also appear to increase objective and subjective sedation, as well as to impair attentional processing, these other cognitive impairments do not appear to fully account for the widespread memory deficits caused by BZ administration. The theoretical and clinical implications of benzodiazepine-induced memory impairments are discussed.

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Mayo Clin Proc. 1993 Aug;68(8):731-7.

Learning and memory impairment in older, detoxified, benzodiazepine-dependent patients.

Rummans TA, Davis LJ Jr, Morse RM, Ivnik RJ.

Department of Psychiatry and Psychology, Mayo Clinic Rochester, Minnesota 55905.

The effects of benzodiazepine dependence on the ability to learn and remember new material (determined with the Auditory-Verbal Learning Test) were studied in 20 detoxified, benzodiazepine-dependent patients who were 55 years of age or older and in a drug-dependence rehabilitation program. The patients were matched approximately for age, sex, and IQ with 20 detoxified, alcohol-dependent patients in the same rehabilitation program and 22 control subjects from a community sample. Neuropsychologic testing was performed a mean of 6 to 10 days after the patients had been completely detoxified from the addicting substance. The benzodiazepine-dependent patients had more difficulty with tests of learning and short-term and delayed recall than did the alcohol-dependent or control group. The difference between the benzodiazepine-dependent patients and the control group was statistically significant. The results suggest that benzodiazepine dependence in older people can cause memory impairment that persists into the early drug-free period.

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Psychol Med. 1994 Feb;24(1):203-13.

Lack of cognitive recovery following withdrawal from long-term benzodiazepine use.

Tata PR, Rollings J, Collins M, Pickering A, Jacobson RR.

Department of Psychology, St George's Hospital Medical School, University of London.

Twenty-one patients with significant long-term therapeutic benzodiazepine (BZ) use, who remained abstinent at 6 months follow-up after successfully completing a standardized inpatient BZ withdrawal regime, and 21 normal controls matched for age and IQ but not for anxiety, were repeatedly tested on a simple battery of routine psychometric tests of cognitive function, pre- and post-withdrawal and at 6 months follow-up. The results demonstrated significant impairment in patients in verbal learning and memory, psychomotor, visuo-motor and visuo-conceptual abilities, compared with controls, at all three time points. Despite practice effects, no evidence of immediate recovery of cognitive function following BZ withdrawal was found. Modest recovery of certain deficits emerged at 6 months follow-up in the BZ group, but this remained significantly below the equivalent control performance. The implications of persisting cognitive deficits after withdrawal from long-term BZ use are discussed.

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Psychol Med. 1988 May;18(2):365-74.

Cognitive impairment in long-term benzodiazepine users.

Golombok S, Moodley P, Lader M.

Institute of Psychiatry, London.

In view of the very extensive and often prolonged use of benzodiazepines in therapeutic practice, this study was designed to investigate whether or not cognitive ability is impaired in long-term benzodiazepine users, and to determine the nature and extent of any deficit. Fifty patients currently taking benzodiazepines for at least one year, thirty-four who had stopped taking benzodiazepines, and a matched control group of subjects who had never taken benzodiazepines or who had taken benzodiazepines in the past for less than one year were administered a battery of neuropsychological tests designed to measure a wide range of cognitive functions. It was found that patients taking high doses of benzodiazepines for long periods of time perform poorly on tasks involving visual-spatial ability and sustained attention. This is consistent with deficits in posterior cortical cognitive function.
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Psychopharmacol Ser. 1988;6:128-39.

The effect of anxiolytic drugs on memory in anxious subjects.

Lucki I, Rickels K.

Department of Psychiatry, University of Pennsylvania, Philadelphia 19104.

The benzodiazepines (BZs), represented by diazepam, are the class of drugs used most frequently to treat clinical anxiety disorders. Since it is known that acute BZ intake impairs memory function, the effects of BZs on memory were evaluated in chronic users of BZ medications. In addition, the acute effects of diazepam were compared with those of the non-BZ anxiolytic buspirone on memory function in anxious subjects. Memory function was evaluated by a free verbal recall procedure where subjects recalled a list of 16 noncategorized nouns immediately after the word list was read (immediate recall) and again 20 min later (delayed recall). When the chronic BZ users were tested for free verbal recall during their first visit, 4-14 h after their last dose, they did not differ in immediate or delayed recall from an age- and sex-matched group of unmedicated anxious subjects. At a subsequent visit, the acute effects of BZ medications were studied 60-90 min after the subjects took their usual dose. Although acute BZ administration did not alter immediate recall, delayed recall was significantly impaired in the chronic BZ users. Thus, complete tolerance does not develop to the acute memory-impairing effects of BZs after long-term use. Acute administration of the anxiolytic drugs diazepam (5 mg) or buspirone (5 or 10 mg) did not alter immediate recall in another group of unmedicated anxious subjects. Diazepam selectively impaired delayed recall of the word list when compared with placebo. In contrast, neither dose of buspirone altered delayed recall. To the extent that such effects on verbal recall tests are reflected in a patient's daily activities, the failure of buspirone to adversely affect memory function could contribute to its usefulness as an alternative antianxiety therapy.
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J Clin Psychopharmacol. 2002 Jun;22(3):285-93.

Long-term benzodiazepine use and cognitive decline in the elderly: the Epidemiology of Vascular Aging Study.

Paterniti S, Dufouil C, Alperovitch A.

Institut National de la Sante et de la Recherche Medicale, Paris, France. paternit@chups.jussieu.fr

Several cross-sectional studies have found cognitive impairment in subjects taking benzodiazepines for long periods. However, it is not known whether long-term use of benzodiazepines accelerates cognitive decline in the elderly. The authors addressed this issue in a follow-up study of 1,389 people aged 60 to 70 years recruited from the electoral rolls of the city of Nantes (Epidemiology of Vascular Aging study). Data on cognitive functioning (five cognitive tests), depressive symptoms (Center for Epidemiologic Studies-Depression Scale), anxiety symptoms (Spielberger Inventory Scale), use of psychotropics and other drugs, and tobacco and alcohol consumption were collected at baseline, 2-year, and 4-year examinations. People reporting to take benzodiazepines at one, two and three examinations were classified as episodic, recurrent, and chronic users, respectively. Among the 1,176 subjects (85%) who participated in the three examinations, the proportions of episodic, recurrent, and chronic users were 10%, 6%, and 7%, respectively. Chronic users of benzodiazepines had a significantly higher risk of cognitive decline in the global cognitive test (Mini Mental State Examination) and the two attention tests than nonusers (Mini Mental State Examination: odds ratio [OR] [95% confidence interval (CI)] = 1.9 [1.0-3.5]; Digit Symbol Substitution test: OR [95% CI] = 2.7 [1.6-4.7]; Trail Making test, part B: OR [95% CI] = 2.1 [1.2-3.7]). Overall, episodic and recurrent users had lower cognitive scores than nonusers, but differences were not statistically significant. These results were independent of age, sex, education, alcohol and tobacco use, anxiety and depression scores, and use of psychotropic drugs other than benzodiazepines. The findings suggest that long-term use of benzodiazepines is risk factor of increased cognitive decline in the elderly.
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Clin Pharmacol Ther. 1998 Dec;64(6):684-92.

Benzodiazepine use and cognitive function among community-dwelling elderly.

Hanlon JT, Horner RD, Schmader KE, Fillenbaum GG, Lewis IK, Wall WE Jr, Landerman LR, Pieper CF, Blazer DG, Cohen HJ.

Department of Medicine, Duke University Medical Center, USA.

OBJECTIVE: To evaluate the relation between benzodiazepine use and cognitive function among community-dwelling elderly. METHODS: This prospective cohort study included 2765 self-reporting subjects from the Duke Established Populations for Epidemiologic Studies of the Elderly. The subjects were cognitively intact at baseline (1986-1987) and alive at follow-up data collection 3 years later. Cognitive function was assessed with the Short Portable Mental Status Questionnaire (unimpaired versus impaired and change in score) and on the basis of the number of errors on the individual domains of the Orientation-Memory-Concentration Test. Benzodiazepine use was determined during in-home interviews and classified by dose, half-life, and duration. Covariates included demographic characteristics, health status, and health behaviors. RESULTS: After control for covariates, current users of benzodiazepine made more errors on the memory test (beta coefficient, 0.35; 95% confidence interval [CI], 0.10 to 0.61) than nonusers. Further assessment of the negative effects on memory among current users suggested a dose response in which users taking the recommended or higher dose made more errors (beta coefficient, 0.57; 95% CI, 0.26 to 0.88) and a duration response in which long-term users made more errors (beta coefficient, 0.39; 95% CI, 0.05 to 0.73) than nonusers. Users of agents with long half-lives and users of agents with short half-lives both had increased memory impairment (beta coefficient, 0.32; 95% CI, 0.01 to 0.64 and beta coefficient, 0.38; 95% CI, 0.02 to 0.75, respectively) relative to nonusers. Previous benzodiazepine use was unrelated to memory problems, and current and previous benzodiazepine use was unrelated to level of cognitive functioning as measured with the other 4 tests. CONCLUSIONS: The results suggested that current benzodiazepine use, especially in recommended or higher doses, is associated with worse memory among community-dwelling elderly.

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Hum Psychopharmacol. 2003 Jan;18(1):51-7.

Cognitive effects of long-term benzodiazepine use in older adults.

Pat McAndrews M, Weiss RT, Sandor P, Taylor A, Carlen PL, Shapiro CM.

Department of Psychology, Toronto Western Hospital and University of Toronto, Canada. mcandrws@uhnres.utoronto.ca

This study examined the potential for cognitive morbidity associated with the long-term use of benzodiazepine (BZ) sedative-hypnotics in a sample of healthy older adults. Tests of memory, attention and processing speed were conducted prior to and 1 month after drug discontinuation for 25 BZ-users and at similar intervals for 26 healthy control subjects. After controlling for differences in affective status between BZ-users and controls, there were no significant group differences in cognitive performance. However, BZ-users showed greater gains on tests of attention and speed of processing at repeat testing compared with controls this improvement was not attributable to a change in affective status. These findings suggest that there may be subtle and reversible effects of long-term BZ use on speed-dependent tasks in older adults. However, the magnitude of these effects is quite small and may be of little clinical significance in the healthy elderly.


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poster:Kon thread:297329
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