So fucked up. Reason number 238 why a surgical cruise ship is a great idea - we won't have to skimp on pain medications. Hell, you can import a 3 mo supply of a med under doctors advice, we could even give 'em prescription meds to bring home. (Although probably there are extra controls on Scheduled substances, which pains meds, of course, are, cuz they make you feel good, and the law doesn't like it when people feel good).
I thought about putting the troll tag on here, but decided that these assertions are objective. It is well documented that its costs fall disproportionately on poor and minorities. The "war on drugs" is, largely, a war on poor, urban, African-Americans. Our jails are full of poor African-Americans. As I've posted before, this creates spillover effects where the deficit of African-American men leads to a breakdown in the traditional social order, specifically less marriage, more single-parent families / kids born out of wedlock, and perpetuating the cycle of poverty.
Obama, who is a clear demonstration that occasional drug use does not ruin a person, could have struck a blow for change by moving, even in small incremental steps, towards drug reform. Instead, he is supporting the hard liners. This is awful, and (unlike many of the other things I complain about), impossible to justify on practical grounds. There is not even the shred of a case that Prohibition II does net good. The empirical evidence is massive - drug use remains high while criminalization has tons of huge negative effects. This is not a supportable policy. It is simply evil.
I might feel bad for the janitors, but if someone blew up a DEA building, I would cheer. It's that bad. Note that there are few if any other parts of government I feel that way about (BATF? Maybe the IRS?) - it's the combination of immorality and horribly net negative consequences (so neither a moral nor consequential defense), enforced by violence & murder, that makes me see red. The other violent parts of the government (say, police and the military) have a mix of good and bad, moral and immoral, positive and negative consequence behavior. I might not like the net result, I might question the career choice, but I don't think they deserve to die. But the DEA murders and jails people to enforce unjust laws that make the world a worse place. If that's not evil, I don't know what is.
ok, now this deserves a troll tag :).
Following the Freedom of Information Act (FOIA), we requested from the FDA all publicly releasable information about the clinical trials for efficacy conducted for marketing approval of fluoxetine, venlafaxine, nefazodone, paroxetine, sertraline, and citalopram, the six most widely prescribed antidepressants approved between 1987 and 1999, which represent all but one of the selective serotonin reuptake inhibitors (SSRIs) approved during the study period. ... Although sponsors are required to submit information on all trials, the FDA public disclosure did not include mean changes for nine trials that were deemed adequate and well controlled but that failed to achieve a statistically significant benefit for drug over placebo. ... we present analyses only for those [four] medications for which mean change scores on all trials were available.Study PDF, via Overcoming Bias
...
Compared with placebo, the new-generation antidepressants do not produce clinically significant improvements in depression in patients who initially have moderate or even very severe depression, but show significant effects only in the most severely depressed patients.
- Music:The Next Episode - Dr. Dre featuring Snoop
![[info]](http://l-stat.livejournal.com/img/userinfo.gif){kind=small}
choiceful & I have a new obsession, courtesy of Mr. Knizia: Lost Cities. So fun! Enough luck to keep things exciting, but still plenty of skill. Are there any other 2 player games that are this good? Our previous mainstay was NetRunner.I have some Betel Nut, anyone have practical experience on how to use it? Apparently you need lime (CaO) in order to activate it, is there any ordinary household food I can use instead?
We're thinking about maybe heading east for the holidays and catching New Years at the Buttery, although it's not yet certain. I'm sort of jonesing for another LA trip, after the last one Shannon started taking a Saturday morning meditation class and I've been stuck home, but I think it's ending soon.
In the evening, we were offered the chance to drop acid for the first time. After some discussion, I was chosen to be the one (can't do both b/c of Tovar, I have wanted to try it for a long time, and other reasons). It was awesome, lots of fun. Energy, metaphors, repression, colors, dancing, talking.
( Read more... )
- Music:For Emily - Amos, Tori
"We made brownies, and I think we're dead."
"Time is going by really really really slow."
"What's the score on the Redwings game?"
via
evwhore comes this 911 call from (audio) a cop who made brownies from confiscated pot and ODed. He avoided charges.- Music:Cathar Rhythem - Era
1: Very bad idea, 2: bad idea, 3: sort of bad idea, 4: eh, 5: maybe ok, 6: probably ok, 7: definitely ok.
Poll #894772 Drugs & Illness
Open to: All, detailed results viewable to: All
Drinking alcohol while you have a cold
Mean: 3.79 Median: 3 Std. Dev 1.77
| 1 |    4 (4.9%) |
| 2 | 19 (23.5%) |
| 3 | 21 (25.9%) |
| 4 | 10 (12.3%) |
| 5 | 8 (9.9%) |
| 6 | 11 (13.6%) |
| 7 | 8 (9.9%) |
Eating pot brownies while you have a cold
Mean: 4.00 Median: 4 Std. Dev 1.78
| 1 | 7 (8.6%) |
| 2 | 8 (9.9%) |
| 3 | 24 (29.6%) |
| 4 | 11 (13.6%) |
| 5 | 9 (11.1%) |
| 6 | 14 (17.3%) |
| 7 | 8 (9.9%) |
Smoking pot while you have a cold
Mean: 2.74 Median: 2 Std. Dev 1.64
| 1 | 20 (24.7%) |
| 2 | 25 (30.9%) |
| 3 | 15 (18.5%) |
| 4 | 9 (11.1%) |
| 5 | 4 (4.9%) |
| 6 | 5 (6.2%) |
| 7 | 3 (3.7%) |
Drinking caffeine while you have a cold
Mean: 4.75 Median: 5 Std. Dev 1.58
| 1 | 2 (2.5%) |
| 2 | 2 (2.5%) |
| 3 | 17 (21.0%) |
| 4 | 16 (19.8%) |
| 5 | 15 (18.5%) |
| 6 | 14 (17.3%) |
| 7 | 15 (18.5%) |
Using an amphetamine (like ecstacy) while you have a cold
Mean: 2.56 Median: 2 Std. Dev 1.51
| 1 | 24 (31.2%) |
| 2 | 18 (23.4%) |
| 3 | 17 (22.1%) |
| 4 | 11 (14.3%) |
| 5 | 1 (1.3%) |
| 6 | 5 (6.5%) |
| 7 | 1 (1.3%) |
Staying out all night partying while you have a cold
Mean: 1.94 Median: 2 Std. Dev 1.29
| 1 | 39 (47.6%) |
| 2 | 27 (32.9%) |
| 3 | 7 (8.5%) |
| 4 | 4 (4.9%) |
| 5 | 2 (2.4%) |
| 6 | 2 (2.4%) |
| 7 | 1 (1.2%) |
- Music:The Boar's Head Carol - Steeleye Span
I ordered some wacky immune boosting stuff from a NZ pharmacy: Buccaline Berna. I was also tempted by Del Immune V, some Russian lactobacillus-based immune booster. Anyone have any stuff like that they recommend?
- Music:Butterfly - Herbie Hancock
Dunno if these abstracts will be useful for anyone else, but just in case...
Drugs 2000 Apr;59(4):865-89
Related Articles, Books, LinkOut
Zolpidem: an update of its pharmacology, therapeutic efficacy and tolerability in the treatment of
insomnia.
Holm KJ, Goa KL
Adis International Limited, Mairangi Bay, Auckland, New Zealand. demail@adis.co.nz
Zolpidem is an imidazopyridine agent that is indicated for the short term (< or = 4 weeks) treatment of insomnia
(recommended dosage 10 mg/day in adults and 5 or 10 mg/day in the elderly or patients with hepatic impairment). Data
have shown that the hypnotic efficacy of zolpidem is generally comparable to that of the benzodiazepines flunitrazepam,
flurazepam, nitrazepam, temazepam and triazolam as well as nonbenzodiazepine hypnotic agents such as zopiclone and
trazodone in the treatment of elderly and adult patients with insomnia. The comparative efficacy of a recently available
nonbenzodiazepine hypnotic zaleplon and zolpidem has yet to be established. There was no evidence of tolerance
developing to the hypnotic effects of zolpidem in a number of studies of up to 6 months' duration. However, tolerance has
been described in a few patients taking the drug at high dosages for periods of up to several years. Zolpidem is well
tolerated in patients with insomnia and the most common adverse events are generally nausea, dizziness and drowsiness.
Although zolpidem produced some psychomotor and memory impairment over the first few hours after administration, it
had few next-day effects (including effects on daytime well-being and morning coordination). In this respect, it was
comparable or superior to flunitrazepam and flurazepam and comparable to other benzodiazepines in patients with
insomnia. Zolpidem appears to have a low potential for abuse. Conclusions: Zolpidem is effective and well tolerated in
patients with insomnia, including the elderly. Studies have shown that zolpidem generally has similar efficacy to other
hypnotics including benzodiazepines and zopiclone. Zolpidem appears to have minimal next-day effects on cognition and
psychomotor performance when administered at bedtime. In addition, there is little evidence of tolerance to the hypnotic
effects of zolpidem, or rebound insomnia or withdrawal symptoms after discontinuation of the drug when it is given as
recommended (10 mg/day for < 1 month) or over longer periods.
PMID: 10804040, UI: 20261185
Placebo-controlled sleep laboratory studies on the acute effects of zolpidem on objective and subjective
sleep and awakening quality in nonorganic insomnia related to neurotic and stress-related disorder.
Saletu-Zyhlarz G, Anderer P, Brandstatter N, Dantendorfer K, Gruber G, Mandl M, Ritter K, Zoghlami
A, Saletu B
Department of Psychiatry, School of Medicine, University of Vienna, Austria.
Recent investigations in our sleep outpatient clinic demonstrated that 30% of patients exhibited organic and 70%
nonorganic sleep disorders, with 41% showing as an additional diagnosis neurotic, stress-related, and somatoform
disorders, 31% affective disorders and 15% mental and behavioral disorders due to psychoactive substance use. Thus, the
aim of the study was to investigate the acute effects of the imidazopyridine zolpidem on objective and subjective sleep and
awakening quality in the largest of the above-mentioned groups. In this single-blind, placebo-controlled cross-over study,
15 patients (9 females and 6 males aged 51.1 + 11. 3 years) diagnosed as having nonorganic insomnia (ICD-10: F 51.0)
related to neurotic and stress-related disorders (F 1.1:12, F 41.2:2 and F 43.2:1) were included. Objective and subjective
sleep and awakening quality measures were investigated in 3 subsequent nights in the sleep laboratory (adaptation,
baseline/placebo and zolpidem 10 mg night), utilizing clinical, polysomnographic, psychometric and psychophysiological
methods. The drug-free patients were matched according to age and sex with 15 normal healthy controls (age 51.2 + 11.8
years). Statistical analysis of polysomnographic variables demonstrated a significant lengthening of the total sleep period
(TSP) and total sleep time (TST), an improvement in sleep efficiency and a shortening of sleep latencies after zolpidem as
compared with placebo. These changes were opposite to the differences between patients and controls. Concerning sleep
architecture, zolpidem increased the length of S4 and S3 + S4 as compared with placebo. Subjective sleep and awakening
quality and the thymopsychic variables drive, mood, affectivity and wakefulness in the morning showed no significant
changes, as a significant improvement had already occurred from the adaptation to the baseline/placebo night. Noopsychic
variables (attention, concentration, attention variability, numerical memory, fine motor activity, reaction time measures)
showed similar findings. Moreover, subjective sleep and awakening quality, thymopsychic and noopsychic measures during
baseline/placebo recordings did not differ significantly from normative data (except for fine motor activity).
Psychophysiological measures did not show any significant alterations either, except for a decrease in systolic blood
pressure in the evening. Conclusion: As compared with placebo, zolpidem induced a significant improvement in objective
sleep quality, mainly by increasing TSP, TST and sleep efficiency and shortening sleep latencies, thereby normalizing the
disorder of initiating and maintaining sleep. Deep sleep stages S3 + S4 increased (although at baseline/placebo these stages
did not differ from controls), while S1, S2 and SREM did not change significantly. Subjective sleep and awakening quality
as well as thymopsychic and noopsychic performance in the morning mainly showed a placebo and 'first- night effect'
phenomenon in these patients. Thus, the changes induced by zolpidem were somewhat different from those after classical
benzodiazepines. Copyright 2000 S. Karger AG, Basel
PMID: 10754428, UI: 20219483
J Int Med Res 1993 Jul-Aug;21(4):171-84
Related Articles, Books, LinkOut
Long-term polysomnographic study of the efficacy and safety of zolpidem in elderly psychiatric
in-patients with insomnia.
Kummer J, Guendel L, Linden J, Eich FX, Attali P, Coquelin JP, Kyrein HJ
Landeskrankenhaus Nordschwarzwald, Fachklinik Psychiatrie, Calw-Hirsau, Germany.
The effects of 20 mg zolipidem were studied in an open, polysomnographically-monitored 179 day trial in 14 elderly
psychiatric patients suffering from severe insomnia. After a placebo run-in of 7 days, zolpidem was given for 179 days
followed by a 30-day wash-out period. Polysomnographic recordings (PSG) were performed just before active
treatment; 30, 90 and 179 days into the treatment period; and at the end of the wash-out period. Statistically significant
improvements in total sleep time, sleep efficiency and percentage of rapid eye movement sleep were observed after 30
days, all of which were maintained at 179 days. Sleep stages 1-4 all changed, with a significant decrease in percentage of
stage 1, and a significant increase in both percentages of stage 2 and 3, and duration of stages 3 and 4 at the end of active
treatment. After a 90-day follow-up period, only stage 3 sleep and sleep efficiency were no longer significantly changed
compared to baseline, all other criteria showing maintenance of efficacy. Slow-wave sleep, which was increased during
active treatment, decreased in the follow-up period. No serious adverse events were observed. These results suggest that,
contrary to other hypnotics, zolpidem, after long-term administration, improves objective sleep parameters and may
normalize a disturbed sleep architecture.
PMID: 8112475, UI: 94156056
J Int Med Res 1999;27(6):253-63
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Zolpidem, a valuable alternative to benzodiazepine hypnotics for chronic insomnia?
Declerck A, Smits M
Centre for Sleep Wake Disorders, Kempenhaeghe Institute, Heeze, The Netherlands.
Sleep quality and anxiety levels were examined using questionnaires and polysomnographic recordings in 22 chronic
insomnia patients who regularly used benzodiazepines to treat their sleeping problems. After abruptly discontinuing their
benzodiazepine medication, patients were randomly allocated to receive either a placebo or zolpidem 10 mg for 1 week,
after which they entered an open extension phase, receiving zolpidem 10 mg for 3 weeks. Subjectively, sleep quality was
considered mediocre during the use of a benzodiazepine hypnotic. One week after the discontinuation, an increase in sleep
latency was observed in the placebo group, whereas zolpidem induced a significant decrease in sleep latency. Deterioration
of other sleep variables (probably rebound) was not suppressed by zolpidem. An explanation for this could be the selective
pharmacological profile of zolpidem. Polysomnographic differences between placebo and benzodiazepine and between
placebo and zolpidem were not reflected by the subjective data on sleep and anxiety. Changes of sleep structure caused by
hypnotics seem not always to be felt as such by patients. After 3-4 weeks of zolpidem treatment, the percentage of
non-rapid eye movement-4 sleep increased significantly, corresponding with a significant subjective improvement of sleep
quality. This indicates that zolpidem may restore physiological sleep.
PMID: 10726234, UI: 20190433
J Int Med Res 1993 Nov-Dec;21(6):306-22
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Pilot controlled double-blind study of the hypnotic effects of zolpidem in patients with chronic
'learned' insomnia: psychometric and polysomnographic evaluation.
Herrmann WM, Kubicki ST, Boden S, Eich FX, Attali P, Coquelin JP
Department of Clinical Psychiatry, Free University of Berlin, Germany.
In a pilot double-blind trial in 21 patients with learned or idiopathic insomnia (DSM-IIIR), patients received placebo for
1 week (nights 1-7), either active (zolpidem, 10 mg) or placebo treatment for 2 weeks (nights 8-21) and then placebo
for a further week (nights 22-28). Variables to measure efficacy, rebound and withdrawal were assessed daily from day
1 to day 28. Polysomnographic recordings together with sleep cycle analysis were performed on nights 7, 21 and 28.
Patients treated with 10 mg zolpidem for 2 weeks had significantly improved sleep efficiency at the end of the
randomised double-blind phase compared with the placebo group. Fractionated sleep-cycle analysis showed an increase
in slow-wave sleep during the first 2-hour cycle after sleep onset. During the withdrawal placebo week, most of the
main sleep variables remained relatively stable in the zolpidem group (nights 22-28), and deteriorated further in the
placebo group. At the end of the withdrawal phase, there was a statistically significant difference between groups, in
favour of the zolpidem treatment, in sleep efficiency, total sleep time, absolute and percentage of time awake, and
percentage of REM sleep. REM sleep, which was normal in both groups at baseline, decreased significantly in the
placebo group between nights 22 and 28 (during the withdrawal placebo week) compared with the zolpidem treatment
group, and the number of periods of time awake increased. Minor subjective complaints were recorded under zolpidem
and were comparable with those under placebo. Zolpidem seemed to improve some important sleep variables, when
assessed both objectively and subjectively. The sleep cycle analysis suggested a possible shift of slow-wave sleep to an
earlier period of the night, with a more physiological sleep structure. There was no evidence for withdrawal or rebound
after stopping the 2 weeks of zolpidem treatment, but rather signs that the effect of zolpidem outlasted active treatment.
The present pilot study justifies a prospective confirmatory comparison of zolpidem with benzodiazepines in an adequate
number of patients and withdrawal after 6-8 weeks of treatment.
PMID: 8143886, UI: 94192840
J Clin Psychiatry 1999 Oct;60(10):668-76
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Zolpidem for persistent insomnia in SSRI-treated depressed patients.
Asnis GM, Chakraburtty A, DuBoff EA, Krystal A, Londborg PD, Rosenberg R, Roth-Schechter B,
Scharf MB, Walsh JK
Department of Psychiatry, Montefiore Medical Center, Bronx, NY 10467, USA.
BACKGROUND: Depressed individuals effectively treated with selective serotonin reuptake inhibitors (SSRIs) often
report persistent insomnia and require adjunctive sleep-promoting therapy. METHOD: Men (N = 40) and women (N =
150) with a mean age of 41.6 years who had persistent insomnia in the presence of effective and stable treatment (at least 2
weeks) with fluoxetine (< or =40 mg/day), sertraline (< or =100 mg/day), or paroxetine (< or =40 mg/day) for DSM-IV
major depressive disorder, dysthymic disorder, or minor depressive disorder of mild-to-moderate severity (and score of <
or =2 on item 3 of the Hamilton Rating Scale for Depression [HAM-D]) participated in this randomized, double-blind,
parallel-group study. At study entry, patients were required to score < or =12 on the HAM-D. During a 1-week
single-blind placebo period, patients had to report on at least 3 nights a latency of > or =30 minutes or a sleep time of <6.5
hours and clinically significant daytime impairment. Patients received either placebo (N = 96) or zolpidem, 10 mg (N =
94) nightly, for 4 weeks and single-blind placebo for 1 week thereafter. Sleep was measured with daily questionnaires and
during weekly physician visits. RESULTS: Compared with placebo, zolpidem was associated with improved sleep: longer
sleep times (weeks 1 through 4, p<.05), greater sleep quality (weeks 1 through 4, p<.01), and reduced number of
awakenings (weeks 1, 2, and 4; p<.05), together with feeling significantly more refreshed, less sleepy, and more able to
concentrate. After placebo substitution, the zolpidem group showed significant worsening relative to pretreatment sleep on
the first posttreatment night in total sleep time and sleep quality, reverted to pretreatment insomnia levels on the other
hypnotic efficacy measures, or maintained improvement (fewer number of awakenings). There was no evidence of
dependence or withdrawal from zolpidem (DSM-IV criteria). Incidence rates of adverse events were similar in both
treatment groups (74% and 83% for placebo and zolpidem, respectively), but 7 zolpidem patients discontinued compared
with 2 placebo patients. CONCLUSION: In this defined patient population, zolpidem, 10 mg, was effectively and safely
co-administered with an SSRI, resulting in improved self-rated sleep, daytime functioning, and well-being.
PMID: 10549683, UI: 20015876
J Psychopharmacol 1999;13(1):81-93
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The safety and tolerability of zolpidem--an update.
Darcourt G, Pringuey D, Salliere D, Lavoisy J
Department of Psychiatry, CHU Pasteur, Nice, France. guy.darcourt@Wanadoo.fr
Zolpidem belongs to a new class of hypnotic agents, chemically distinct from the pre-existing ones, and has a unique
neuropharmacological profile. It induces sedative/hypnotic effects in rodents at doses much lower than those for
anticonvulsant and myorelaxant activities. Clinically, zolpidem is indicated for the short term treatment of insomnia. It
has a short half-life (2.4h), with no active metabolite, and does not accumulate during repeated administration. The
pharmacokinetic profile associated with the absence of active metabolites is consistent with the short duration of action
and absence of residual effects that have been observed. Polysomnographic experience indicates that zolpidem induces a
sleep pattern which is similar to that of physiological sleep, and which produces either no or only minimal effects on
sleep architecture after abrupt discontinuation. Aspects of the general safety of zolpidem have been studied in data
obtained from healthy volunteers and patients, both adult and elderly, during its clinical development and in
post-marketing experience. Zolpidem appears to be well-tolerated in adults and in the elderly, when administered in
accordance with prescribing instructions. The available data indicate that, in these circumstances, the risk of abuse or
dependence is minimal.
PMID: 10221362, UI: 99236551
Clin Neuropharmacol 1997 Jun;20(3):253-63
Related Articles, Books, LinkOut
Multidrug comparison (lorazepam, triazolam, zolpidem, and zopiclone) in situational insomnia:
polysomnographic analysis by means of the cyclic alternating pattern.
Parrino L, Boselli M, Spaggiari MC, Smerieri A, Terzano MG
Institute of Neurology, University of Parma, Italy.
Since homogeneous samples of insomniacs are difficult to recruit for pharmacotherapy studies, normal sleepers can be
used to assess the protective effect of hypnotic drugs, under standardized nonconducive conditions. In particular, a noisy
environment is a typical cause of situational insomnia that can be counteracted by a sedative-hypnotic agent. Six healthy
middle-aged subjects (three men and three women), with no complaints about sleep, underwent a completely randomized
double-blind series of 10 nocturnal polysomnograms with at least 72-h washout intervals. All subjects received a single
dose of placebo, zolpidem 10 mg, zopiclone 7.5 mg, lorazepam 1 mg, and triazolam 0.25 mg both under basal and
under perturbed conditions. For each individual, five recordings were carried out under basal conditions (sound
pressure level not higher than 30 dB) and five recordings under acoustically perturbed conditions (continuous white
noise at 55 dB). Sleep quality was assessed by means of a visual analogue scale (VAS). All recordings were scored
according to conventional rules (macro-structure) and cyclic alternating pattern (CAP) methodology (microstructure).
Statistical analysis was based on a repeated measures analysis-of-variance design integrated by Bonferroni adjusted
probabilities. Under placebo, situational insomnia was confirmed by the significant increase in sleep fragmentation
(intrasleep wakefulness) and by the significant enhancement of arousal instability (CAP parameters). In contrast to
macrostructural information, CAP parameters were highly sensitive in detecting the perturbing effects of noise (mean
CAP rate under placebo, 57%) and the protective action of hypnotic drugs during perturbation (mean CAP rate under
active medication, 41%). Microstructural analysis enabled us to discriminate hypnotic drugs from placebo,
nonbenzodiazepine compounds from benzodiazepine agents, and zopiclone from zolpidem. The latter, in fact, induced
the lowest values of CAP rate both under basal (30%) and under noisy (39%) conditions and determined a significant
decrease in electroencephalogram arousals. All CAP parameters were significantly correlated with the
visual-analogue-scale scores for sleep quality. The use of CAP methodology in a highly standardized model of
situational insomnia can be a valid alternative to conventional sleep scoring for the investigation of drug effects on
disturbed sleep.
PMID: 9197949, UI: 97341657
Clin Neuropharmacol 1997 Apr;20(2):116-25
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Minimal rebound insomnia after treatment with 10-mg zolpidem.
Ware JC, Walsh JK, Scharf MB, Roehrs T, Roth T, Vogel GW
Sleep Disorders Center, Sentara Norfolk General Hospital, VA 23507, USA.
This study examined rebound insomnia after discontinuation of chronic use of zolpidem (10 mg), a short elimination
half-life imidazopyridine. The zolpidem group was bracketed by a placebo group and a positive control group taking
0.5 mg of triazolam (twice the recommended dose), which is known to produce rebound insomnia. Ninety-nine patients
with sleep complaints that were polysomnographically documented participated in the study. After randomization,
patients completed a 2-night, single-blind, placebo baseline period, a 28-night double-blind treatment phase, and a
3-night, single-blind, placebo substitution period. Polysomnographic and subjective sleep variables indicated a lack of
rebound insomnia for the zolpidem group. The positive triazolam control group had rebound insomnia only on the first
discontinuation night. There was no significant correlation between rebound insomnia and the level of initial insomnia,
the degree of response to treatment in week 4, or the amount of tolerance that developed during drug use. During the
4-week treatment period, efficacy diminished for both drugs. From these data, it cannot be determined whether the lack
of rebound insomnia with zolpidem is a result of drug dose or some property of the drug such as receptor selectivity.
PMID: 9099463, UI: 97254228
Int Clin Psychopharmacol 1996 Dec;11(4):255-63
Related Articles, Books, LinkOut
Sleep in patients with chronic primary insomnia during long-term zolpidem administration and after
its withdrawal.
Monti JM, Monti D, Estevez F, Giusti M
Department of Pharmacology and Therapeutics, Clinics Hospital, Montevideo, Uruguay.
A double-blind trial was carried out to determine the effect of zolpidem or a placebo on sleep in two groups of
insomniac patients with a diagnosis of moderate chronic primary insomnia. Zolpidem was given at a daily dose of 10 mg
for 27 nights and was preceded (two nights) and followed (three nights) by a placebo. Zolpidem induced a significant
increase of total sleep time, while total wake time and wake time after sleep onset were reduced. Values corresponding
to stage 2 sleep were augmented, while stage 3 sleep and REM sleep showed no significant changes. Tolerance did not
develop during the zolpidem administration period, and rebound insomnia did not show following abrupt interruption
of drug administration. In addition, patients on zolpidem had a more peaceful sleep with no decrement of levels of
alertness.
PMID: 9031992, UI: 97184032
Ann Clin Psychiatry 1996 Jun;8(2):89-91
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Zolpidem-induced psychosis.
Markowitz JS, Brewerton TD
Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston 29425-0810,
USA.
Zolpidem is reported to be a safe and effective hypnotic agent for the short-term treatment of insomnia. There are
several case reports of zolpidem causing psychotic reactions in patients with no history of psychosis. We report two
additional cases in which zolpidem was implicated in psychotic reactions characterized by auditory and visual
hallucinations as well as delusional thinking. Both patient's symptoms resolved with the discontinuation of zolpidem use.
It appears that our cases share several features in common with the other reported cases. All were female, there
appeared to be some dose dependency involved, and the adverse event resolved fairly quickly upon zolpidem
discontinuation. Zolpidem should be used at the lowest effective dose for the least amount of time as necessary. Female
patients may possibly require smaller doses. In patients manifesting new-onset or unexplained psychotic symptoms,
zolpidem use should be considered in the differential diagnosis.
PMID: 8807033, UI: 96400657
Drug Saf 1995 Oct;13(4):257-70
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An assessment of short-acting hypnotics.
Mendelson WB, Jain B
Department of Neurology, Cleveland Clinic Foundation, Ohio, USA.
Insomnia, the experience of poor quality or quantity of sleep, is a very common complaint. Approximately 65 million
adults (36% of the American population) complain of poor sleep, and of this group, 25% have insomnia on a chronic
basis. These chronic insomniacs not only report higher rates of difficulty with concentration, memory and the ability to
cope with minor irritations but also have 2.5 times more fatigue-related automobile accidents than do good sleepers.
Despite its ubiquity, insomnia is often either untreated or inadequately treated. Short-acting hypnotics are advocated for
transient insomnia, which lasts less than 3 weeks, and in patients with chronic insomnia as an adjunctive treatment where
nonpharmacological treatment is not sufficient to alleviate insomnia and the related daytime detrimental effects. The
putative adverse effects of hypnotics must be weighted against the severe health effects caused by continued sleep
impairment. If hypnotic agents are used, they should be taken nightly only for brief use, or intermittently in longer
term use. Benzodiazepines, zolpidem and zopiclone (in countries where the latter is available) remain the recommended
hypnotic agents, although in the past few years there has been much criticism in lay magazines and on television about
the use of benzodiazepines. However, this review of the efficacy and tolerability data of the short-acting hypnotics
suggests that triazolam is comparable with other short-acting hypnotics at equipotent doses while taking into
consideration that for every hypnotic, different study populations display different degrees of efficacy. In addition,
contrary to previous suggestions that such adverse effects are rebound insomnia and anterograde amnesia are unique to
triazolam, hypnotically equivalent doses of tirazolam have not been shown to produce these effects more frequently than
other short-acting hypnotics. The newer nonbenzodiazepine hypnotics seem to be equally efficacious as the short-acting
benzodiazepines; whether they will truly have a better adverse effect profile will be determined as more clinical
experience accumulates. Despite the availability, relative safety and efficacy of these newer hypnotic agents, they should
not be perceived as the sole treatment for insomnia and should be used in conjunction with nonpharmacological
techniques (such as adherence to good sleep hygiene, sleep restriction, stimulus control and biofeedback therapy).
PMID: 8573298, UI: 96127552
Clin Psychiatry 1994 May;55(5):192-9
Related Articles, Books, LinkOut
A multicenter, placebo-controlled study evaluating zolpidem in the treatment of chronic insomnia.
Scharf MB, Roth T, Vogel GW, Walsh JK
Center for Research in Sleep Disorders, Mercy Hospital of Hamilton, Fairfield, Cincinnati, Ohio 45246.
BACKGROUND: Zolpidem is a short-acting, nonbenzodiazepine hypnotic with rapid onset of action. Even though it is
not a benzodiazepine, it binds to one of three types of central benzodiazepine receptors, showing selective binding to the
type 1 benzodiazepine receptor subtype. Therapeutic hypnotic dosages do not disturb normal sleep patterns (sleep
architecture). METHOD: A randomized, double-blind, placebo-controlled, parallel group multicenter trial was
conducted to determine the effectiveness of 10 mg and 15 mg of zolpidem in the long-term (35 nights) treatment of
chronic insomnia in 75 patients. Sleep stage effects and motor and cognitive effects during the 35-night treatment period
and the 3-night posttreatment period were also investigated. RESULTS: Within the first week of treatment, 10 mg of
zolpidem had a significant effect on latency to persistent sleep and sleep efficiency. Efficacy was maintained throughout
the 35 nights of drug administration. There was no evidence of residual effect with 10 mg of zolpidem. Stage 3-4 sleep
was preserved at both the 10-mg and 15-mg zolpidem dosages. There was no evidence of tolerance at either dose and no
significant treatment differences between the 10-mg zolpidem group and placebo in latency to persistent sleep or sleep
efficiency during the posttreatment period. Also, the 10-mg zolpidem dosage was judged by the patients to have helped
them fall asleep. Similar results were observed with the 15-mg zolpidem dosage. However, there were significant
decreases in REM sleep at Weeks 3 and 4 with 15 mg of zolpidem compared with placebo. Overall, incidence rates of
treatment-emergent adverse events in the zolpidem groups were similar to those in the placebo group. CONCLUSION:
This is the first sleep laboratory study using a parallel placebo group to demonstrate efficacy for longer than 4 weeks
with a hypnotic agent. In this study 10 mg of zolpidem was found to be safe and effective for the long-term treatment of
chronic insomnia, demonstrating hypnotic efficacy without affecting sleep stages or producing tolerance effects,
rebound effects, or detrimental effects on psychomotor performance. The 15-mg zolpidem dosage provided no clinical
advantage over the 10-mg zolpidem dosage.
PMID: 8071269, UI: 94350876
Thanks to a tip from Michelle, I recently read a bit of the book Driven by Distraction. I identifed very strongly with some of its case studies, and then took an online ADD test, resulting in the realization that I have (mild) Hyperactive ADD. Unlike the attitude I saw in DBD, I don't feel that this absolves me of any responsibility for my actions, successes, or failures. Still, it is interesting to know that there are lots of other people out there who suffer from some of the same difficulties I do: an inability to stay focused on one thing, starting many projects and not finishing them, getting bored easily, having their mind race when they try to relax, difficulty sitting still, lots of trouble with organization, difficulty doing mundane tasks like paying bills and doing taxes, etc. Being practical, the main thing I want to know is what to do about it. I am into using chemicals (drugs, nutrients) to alter behavior, so I looked there for a potential "quick fix" (although they rarely exist).
I happen to know a fair amount about neurochemistry and drugs for altering neurochemistry (just something I'm interested in), and I found it quite strange that Ritalin, an old drug with substantial physical side effects, is the standard treatment. While the stimulants seem to be quite effective at treating ADHD, I am concerned that short-term effectiveness is an easily seen benefit, while long-term problems are a harder to see cost, resulting in incorrect calculations as to their utility. The legal stimulants, like their illegal cousins cocaine and methamphetamine, may well cause long-term effects on the body and brain, and their long-term efficacy has been called into doubt. Here is a page of references I found on the subject.
One of the neat things which has happened in the past few decades is that we've discovered all sorts of drugs which affect the brain without affecting the body. I understand that lots of people feel that taking drugs is bad, and that taking drugs for ADD is bad, and I have no disagreement with that (here is a quick summary of the scientific evidence on alternative treatments). What I am curious about is, for those people who do choose drug therapy, if there are better drugs that they can use (more effective or fewer side effects).
Some of the theories on ADHD have to do with neurochemical imbalances, as explained in this useful site, for example. The effects appear to be complicated. As the above page says: "No single neurotransmitter deficiency appears to explain fully the array of medications which improve symptomatology in AD/HD. The single neurotransmitter concept is refuted by the inability of specific medications known to modulate individual neurotransmitters to improve symptoms. It is possible that AD/HD is due to imbalance of multiple inter-related neurotransmitters." Also "This would suggest that both norepinephrine and dopamine are involved in the etiology of AD/HD but attention was primarily mediated via dopamine pathways" , and "This would support the hypothesis that specific behavioral components of AD/HD are mediated by different neurotransmitter pathways." The genes that have been found so far that seem to be linked with ADD are related to the dopamine system. "While most neuroscientists and neuroscience wannabes are hesitant to reduce anything to a simple equation or catch phrase we might be on fairly firm ground in saying that attention problems may be seen as a dopamine deficiency." (from here).
Two of the most important drive/motivational related neurotransmitters are dopamine and noradrenaline (norepinephrine). It is thought that ADDers may be deficient in dopamine. The stimulants used to treat ADD all increase the release and inhibit the reuptake of dopamine. However, this is not the sole explanation, as L-dopa (the precursor to dopamine, which increases dopamine levels) does not help treat ADD, and some dopamine antagonists show modest benefits. Increasing noradrenaline is, unsurprisingly, also another way to treat ADD. Clonidine boosts some specific noradrenergic activity, as do some other drugs (such as the stimulants). "a change in noradrenergic function appears to be a necessary but not sufficient condition for improvement of AD/HD symptoms." (from here)
The current drugs used are:
Methylphenidate (Ritalin):
http://hsc.virginia.edu/medicine/clinica
http://www.rxlist.com/cgi/generic/methph
Dextroamphetamine (Dexedrine):
http://hsc.virginia.edu/medicine/clinica
http://www.rxlist.com/cgi/generic/dextro
Clonidine (Catapress):
http://hsc.virginia.edu/medicine/clinica
http://www.rxlist.com/cgi/generic/clonid
Since ADHD seems related to dopamine and noradrenaline, rather than the "dirty" stimulants, I would consider drugs such as NARI's, eugeroics (alpha-2-adrenergics), and dopamine boosters. Using PubMed, I set out to see whether research had been done on these compounds. It turns out that the medical establishment has done a fair bit experimentation with non-stimulant pharmacological treatment of ADHD. Summaries can be found here and here. Following are some of the specific drugs that seemed promising to me, given my general knowledge of neurochemistry, along with the research that has been done so far.
- Dopamine boosters:
- Bupropion
(Wellbutrin):
While bupropion's method of action is not fully understood, it is not a MAOI, but seems to inhibit the reuptake of dopamine. It is marketed as an antidepressant and an aid to stop smoking. There has been some clinical research, and it seems to work pretty well (ref1, ref2). However wellbutrin does have some side effects, and it has not been accepted by the mainstream. - Selegiline
(deprenyl)
Selegiline is an irreversible selective MAO-B inhibitor, which is used to treat Parkinson's and for life-extension purposes. It prevents dopamine from being broken down by monoamine oxidase-B. In an animal model, it was found to prevent the impulsiveness component of ADHD. It has shown effectiveness in human treatment in some trials (also here), but other trials showed no effectiveness. For some reason it seems to be most often tested on those with ADHD & Tourette's syndrome.
- Bupropion
(Wellbutrin):
- Noradrenaline boosters:
- Reboxetine / Tomoxetine
(Reboxetine
description and research)
Reboxetine has been FDA-declined in the USA (despite being approved in many other countries and used for years), but a very similar compound called tomoxetine is being tested on ADHD in the states and is showing great promise. The conspiracy theory is that the FDA did not approve reboxetine so that Eli Lilly (makers of Prozac), who have the patent on tomoxetine, can have the FDA-approved NARI. Whether or not this is true, tomoxetine has had excellent results in the recent studies (ref1, ref2) on using it to treat ADHD. It will probably be FDA-approved for treatment of ADHD, but until then, people who wish to use a NARI can get reboxetine from a non-US online pharmacy.
- Reboxetine / Tomoxetine
(Reboxetine
description and research)
- Eugeroics:
- Modafinil / adrafinil
These are selective/specific noradrenaline antagonists. Modafinil is FDA-approved in the US for treatment of narcolepsy, and is notable for its lack of adverse effects on sleep, unlike amphetamines. In two studies, one on kids and one on adults, it was found effective for ADHD.
- Modafinil / adrafinil
The good news is that in support of my intuition, positive results have been found for most of these drugs. The bad news is that none of them are well established as methods for ADHD treatment. Other than tomoxetine, all of them have been around for years. I can only speculate as to the reasons for this, inertia and conservativeness seem like the most likely explanations. I suspect it is much easier for the makers of ritalin to maintain/increase their market share than for the makers of other drugs to break in. Many doctors are conservative about trying new drugs, and prefer to stick to things which they cannot be questioned for prescribing. In general, mainstream treatments seem to change pretty slowly. Still, with the current backlash against ritalin (due to it being overprescribed as well as unsafe), perhaps the window is open. And regardless of what the establishment does, if you or a loved one has ADHD and are the sort of person who likes to research the drugs he takes and pick the best ones, rather than just asking a doctor, you should find this information useful.
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