Rev Neurol 2001 Feb 1-15;32(3):247-50
[Article in Spanish]
Mauri-Llerda JA, Tejero-Juste C, Iniguez C, Morales-Asin F.
Servicio de Neurologia, Hospital Clinico Universitario Lozano Blesa, San
Bosco, 15. E-Zaragoza 50009.
OBJECTIVE: To review the current treatment and usefulness of lamotrigine
absence seizures. DEVELOPMENT: Absence seizures are classified amongst the
generalized epilepsies. They are defined as a transient loss of
sudden onset and recovery characteristically associated with generalized
spike-and-wave discharges on the EEG. In recent years, the epileptic
associated with this type of seizure have been better defined, basically
means of video-EEG studies. The International League Against Epilepsy has
recognized four epileptic syndromes with typical absences: absence-epilepsy
of childhood, juvenile absence-epilepsy, juvenile myoclonic epilepsy and
with myoclonic absences. The classical treatment for this type of seizure
based on ethosuximide, or more often, sodium valproate. Sometimes both
together were necessary. Other useful drugs are the benzodiazepines such
as clobazam. CONCLUSIONS: We review studies of the efficacy and tolerance of
lamotrigine in the treatment of absence seizures, one of the groups of
in which this drug has been shown to be most effective. Although studies
comparing lamotrigine, valproate and ethosuximide are necessary, we
the possibility that lamotrigine may be a drug of choice in absence
2: Rev Neurol 2001 Jan 1-15;32(1):77-82
[Article in Spanish]
Mauri-Llerda JA, Pascual-Millan LF, Tejero-Juste C, Iniguez C, Escalza-Cortina
I, Morales-Asin F.
Servicio de Neurologia, Hospital Clinico Universitario Lozano Blesa,
Zaragoza, Espana. email@example.com
OBJECTIVE: The neuropsychological assessment of the epileptic patient is a
important aspect of diagnosis and treatment. It may be used to contribute
localization of the hemisphere involved in the seizures, differentiate
situations of anxiety or depression or when planning treatment for
rehabilitation. We review the different aspects of neuropsychological
patients with epilepsy. DEVELOPMENT: Firstly we review the different tests
in the neuropsychological assessment of epilepsy. Dodrill's
battery of tests, in which the patients score less than the controls, is
most commonly used. We then evaluate and study the so-called 'transient
cognitive disorder'. We also study memory problems in epilepsy. There may
episodes of seizures with amnesic features ('amnesic epileptic seizures').
Finally, the possibility of neuropsychological dysfunction secondary to
antiepileptic drugs should always be considered. CONCLUSIONS: Epileptic
have lower scores than persons taken as controls for the results of
neuropsychological tests, although there is less difference between the
groups when the patient group is made up of persons with a normal
intelligence quotient. Transient cognitive involvement is common in epileptics and may
underachievement at school or psychological problems. Memory disorders,
particularly subjective, are common in epileptics, although
tests other than those generally used may be necessary to evaluate this.
possible that such memory disorders, if occurring as seizures, may be due
amnesic partial crises, which should always be differentiated from the
of transient global amnesia. Almost all antiepileptic drugs can cause
neuropsychological effects, especially the benzodiazepines and
3: Sleep 2000 Feb 1;23 Suppl 1:S39-47
Nonselective and selective benzodiazepine receptor agonists--where are we
Department of Neuropharmacology, The Scripps Research Institute, La Jolla,
92037, USA. firstname.lastname@example.org
Insomnia is problematic for many individuals, causing them to seek
There is a long history of therapies aimed at restoring normal sleep
each having its advantages and disadvantages. This review traces the
insomnia drug therapies from chloral hydrate and the barbiturates through
benzodiazepines and explores the newest selective benzodiazepine receptor
agonists, including zolpidem and zaleplon. The mechanisms of action of the
benzodiazepine receptor agonists are compared and contrasted. A
comparison is presented showing the importance that parameters such as
onset of action, lipophilicity, metabolites, half-life, and receptor-binding
affinity have on clinical effects. The possible adverse effects of sleep
are discussed, including residual sedation and psychomotor impairment,
daytime anxiety, anterograde amnesia and cognitive impairment, rebound insomnia,
drug tolerance and dependence. Effects on sleep efficiency and staging are
also discussed. Recommendations for the primary care physician on the selection
hypnotics are also provided. Benzodiazepine receptor agonists are often
appropriate agents in the treatment of insomnia; however, individual drug
patient considerations are important in matching the most appropriate
the individual patient. Zolpidem and zaleplon, newer selective
receptor agonists, offer additional treatment options.
4: Am Fam Physician 2000 Apr 1;61(7):2121-8 [Texto
Addiction: Part I. Benzodiazepines--side effects, abuse risk and
Longo LP, Johnson B.
University of Wisconsin Medical School, Milwaukee, USA.
Benzodiazepines are widely prescribed for a variety of conditions,
anxiety and insomnia. They are relatively safe and, with overdose, rarely
in death. However, used chronically, benzodiazepines can be addicting.
agents are often taken in combination with other drugs of abuse by
addiction disorders. In such patients, alternatives to benzodiazepines may
preferable and may include antidepressants, anticonvulsants, buspirone,
antihypertensive agents and the newer neuroleptic medications. Caution
used when prescribing benzodiazepines to patients with a current or remote
history of substance abuse.
5: CMAJ 2000 Jan 25;162(2):225-33 [Texto
Meta-analysis of benzodiazepine use in the treatment of insomnia.
Holbrook AM, Crowther R, Lotter A, Cheng C, King D.
Centre for Evaluation of Medicines, St. Joseph's Hospital, Hamilton, Ont.
OBJECTIVE: To systematically review the benefits and risks associated with
use of benzodiazepines to treat insomnia in adults. DATA SOURCES: MEDLINE
the Cochrane Controlled Trials Registry were searched for English-language
articles published from 1966 to December 1998 that described randomized
controlled trials of benzodiazepines for the treatment of insomnia. Key
included "benzodiazepines" (exploded), "randomized
controlled trial" and
"insomnia." Bibliographies of relevant articles were reviewed
studies and manufacturers of benzodiazepines were asked to submit
randomized controlled trial reports not in the literature. STUDY SELECTION:
Articles were considered for the meta-analysis if they were randomized
controlled trials involving patients with insomnia and compared a
with placebo or another active agent. Of the 89 trials originally
met our criteria, representing a total of 2672 patients. DATA EXTRACTION:
were extracted regarding the participants, the setting, details of the
intervention, the outcomes (including adverse effects) and the
quality of the studies. DATA SYNTHESIS: The meta-analyses of sleep records
indicated that, when compared with placebo, benzodiazepines decreased
latency by 4.2 minutes (non-significant; 95% confidence interval (CI -0.7
9.2) and significantly increased total sleep duration by 61.8 minutes (95%
37.4 to 86.2). Patient-reported outcomes were more optimistic for sleep
those randomized to benzodiazepine treatment estimated a sleep latency
of 14.3 minutes (95% CI 10.6 to 18.0). Although more patients receiving
benzodiazepine treatment reported adverse effects, especially daytime
and dizziness or light-headedness (common odds ratio 1.8, 95% CI 1.4 to
dropout rates for the benzodiazepine and placebo groups were similar.
function decline including memory impairment was reported in several of
the studies. Zopiclone was not found to be superior to benzodiazepines on any
outcome measures examined. INTERPRETATION: The use of benzodiazepines in
treatment of insomnia is associated with an increase in sleep duration,
is countered by a number of adverse effects. Additional studies evaluating
efficacy of nonpharmacological interventions would be valuable.
6: Eur Neuropsychopharmacol 1999 Dec;9 Suppl 6:S407-12
Eur Neuropsychopharmacol. 1999 Dec;9 Suppl 6:S391-2
The use of benzodiazepines in anxiety and other disorders.
Argyropoulos SV, Nutt DJ.
Psychopharmacology Unit, School of Medical Sciences, University of
Benzodiazepines have come under scrutiny and attack over recent years
their abuse liability, withdrawal reactions and development of tolerance.
Consequently, practitioners worldwide are discouraged from prescribing
While some of these risks may have been exaggerated, benzodiazepines
useful therapeutic tool, alone or in combination, in a number of
medical conditions. Withholding such treatment may be unjustified and
detrimental to the patients' health. Further, benzodiazepines have helped
researchers in their attempts to elucidate the neurobiological mechanisms
underlying anxiety. This, in return, leads to the development of new
anxiolytic treatments, with fewer problems compared to the traditional
benzodiazepine compounds. Such new agents are already available or at the
closing stages of clinical trials.
7: Can J Clin Pharmacol 1999 Winter;6(4):185-6
Benzodiazepines: the science and the myths.
Centre for Addiction and Mental Health, Toronto, Canada.
8: J Clin Psychopharmacol 1999 Dec;19(6 Suppl 2):23S-29S
International study of expert judgment on therapeutic use of
other psychotherapeutic medications: IV. Therapeutic dose dependence and
liability of benzodiazepines in the long-term treatment of anxiety
Uhlenhuth EH, Balter MB, Ban TA, Yang K.
Department of Psychiatry, University of New Mexico School of Medicine,
Albuquerque 87131, USA. email@example.com
Despite decades of relevant basic and clinical research, active debate
about the appropriate extent and duration of benzodiazepine use in the
of anxiety and related disorders. The primary basis of the controversy
be concern among clinicians, regulators, and the public about the
potential and the abuse liability of benzodiazepines. This article reports
systematically elicited judgments on these issues by a representative
73 internationally recognized experts in the pharmacotherapy of anxiety
depressive disorders, a panel which was constituted by a multistage
peer nomination. The criterion for inclusion at each stage was the
at least two peers as one of the "professionally most respected
the world with extensive experience and knowledge in the pharmacotherapy
anxiety and depressive disorders." Sixty-six respondents (90%)
comprehensive questionnaire covering a wide range of topics relevant to
therapeutic use of benzodiazepines and other medications that might be
the same purposes. Overall, the expert panel judged that benzodiazepines
higher risk of dependence and abuse than most potential substitutes but a
risk than older sedatives and recognized drugs of abuse. There was little
consensus about the relative risk of dependence and abuse among the
benzodiazepines. Differences between benzodiazepines with shorter and
longer half-lives in inducing withdrawal symptoms are much less clear during
than during abrupt discontinuation. There was little agreement about the
important factors contributing to withdrawal symptoms and failure to
discontinue benzodiazepines. The pharmacologic properties of the medication may be the
important contributors to withdrawal symptoms. In contrast, the clinical
characteristics of the patient may be the most important contributors to
to discontinue medication. The experts' judgment seems to support the
use of benzodiazepines for the treatment of bona fide anxiety disorders,
over long periods. The experts generally viewed dependence and abuse
as clinical issues amenable to appropriate management, as for other
events related to therapy. However, more definitive clinical research on
remaining controversial issues is urgently needed to promote optimal
Consensus development conference
9: J Clin Psychopharmacol 1999 Dec;19(6 Suppl 2):17S-22S
Psychological strategies for discontinuing benzodiazepine treatment.
Center for Anxiety and Related Disorders, Boston University, Massachusetts,
Successful discontinuation of therapeutic drugs requires patients to
two potentially difficult phases. First, they must complete the drug
discontinuation procedure itself, which may entail coping with rebound and
withdrawal symptoms as well as anxiety due to stopping a treatment on
depend psychologically. Second, they must maintain drug abstinence over
despite possible exacerbations or recurrences of the disorder that the
drug was treating. For optimal success, interventions aimed at assisting patients
discontinue drug use must address both of those tasks. Patients' ability
discontinue benzodiazepines seems to be strongly influenced by cognitive
appraisals of the threat represented by symptoms and of their own
cope with it without medication. For problems of that kind, cognitive and
behavioral techniques such as those developed for the treatment of panic
disorder may be especially well-suited. Currently, the most successful
approaches to benzodiazepine discontinuation include the following
(1) assisting with initial drug discontinuation, educating patients about
benzodiazepine dependence and withdrawal, and about the kinds of symptoms
can emerge as the drug dose is decreased, combined with a flexible drug
conducted in supportive collaboration with the patient; and (2) dealing
exacerbations of the illness, and providing disorder-specific cognitive-behavioral treatment as an alternative to the resumption of
pharmacotherapy. It seems to be crucial that the drug taper be completed
psychological treatment concludes.
10: J Clin Psychopharmacol 1999 Dec;19(6 Suppl 2):2S-11S
Effectiveness and safety of benzodiazepines.
Psychiatric Hospital, Ludwig-Maximilians University, Munich, Germany.
Benzodiazepines have been used to treat a wide variety of disorders,
generalized anxiety disorder, panic disorder, sleep disorders,
disorders, and depression. Concerns regarding physiologic dependence,
withdrawal, and abuse potential with benzodiazepines prompted the
strict guidelines for the use of these agents. Studies have shown that the
of physiologic dependence increases with factors such as the dose of the
benzodiazepine used and the duration of treatment. Restrictions involving
benzodiazepines have led to the substitution of alternative medicines that
have decreased efficacy and greater safety concerns. There is a need for a
balanced assessment of the benefits and risks associated with
to ensure that patients who would truly benefit from these agents are not
11: J Clin Pharm Ther 1999 Oct;24(5):347-55
Clinically significant pharmacokinetic drug interactions with
Institute of Community Medicine, University of Tsukuba, Japan.
The reports of interactions between benzodiazepines (BZPs) and other drugs
(e.g., antidepressants, selective serotonin reuptake inhibitors, antiulcer
drugs, antiepileptic drugs, macrolide antibiotics) during their combined
reviewed. In general, metabolism of BZPs is delayed when combined with a
of other drugs but some reports have suggested otherwise. In recent years,
cytochrome P450 (P450 or CYP) isoenzyme that catalyses the metabolism of
has also been identified. BZPs are mainly catalysed by CYP3A4. When
reports are studied, it appears necessary to be exceptionally careful
interactions mainly between BZPs and selective serotonin reuptake
cimetidine, antiepileptic drugs, macrolide antibiotics and antimycotics.
information is necessary to identify individuals at greatest risk of drug
interactions and adverse events.
12: Support Care Cancer 1999 Nov;7(6):379-85
Support Care Cancer. 1999 Nov;7(6):371-2
Psychopharmacology in supportive care in cancer: a review for the
Stiefel F, Berney A, Mazzocato C.
Service de Psychiatrie de Liaison, CHUV, CH-1011 Lausanne, Switzerland.
Benzodiazepines are widely utilized in the cancer setting. Most aspects
to their use in supportive care are reviewed to assist the clinical
in prescribing such drugs. This review covers pharmacokinetics,
adverse effects and drug interactions, and compares the profiles of
benzodiazepines. Finally, controversial issues with regard to