Re: Lorazepam Chopping/Dosing
Originally Posted by
Sox
What is the best anxiety controlling dose for Lorazepam that would reduce the chances of major dependency until I can get back to my GP?
That horse has probably already bolted. You're best option is probably to ignore the dependency issue for the moment as getting the anxiety under control is more important. Once stabilized on an effective treatment, AD and/or therapy, you can begin working on tapering off preferably by switching to a longer half-life benzodiazepine (BZD) such as diazepam (Valium). In fact I'd be asking to switch to diazepam now as the longer half-life BZDs are slower to induce dependency.
An alternative to BZDs worth trying is pregabalin (Lyrica). It has essentially the same effect on the brain as the BZDs, but achieves it by a different mechanism. While dependency is also an issue it usually takes longer to develop. Unlike the BZDs it appears not to worsen anxiety and depression (see below) and may hasten AD onset a little.
1mg as a last resort, or a maintenance dose of a quarter tablet 3 or 4x a day?
Lorazepam has a half-life of about 12 hours - range 10-20 hours - so you should only need to take it twice a day at an effective dose.
A few things to keep in mind, many people, including doctors, tend to hyperventilate about BZD dependency yet don't have the same concerns about antidepressants some of which can be at least as hard to quit. Secondly, everyone on the planet is already dependent on BZDs. Diazepam and its metabolites, also lorazepam, are a natural constituent of all foods [1]. They probably started out as a plant poison to which all animal life is now dependent. Our brains need BZDs to function and the only source is the food we eat. While the quantities we get from food are small, they are not insignificant. Food derived BZD levels can reach pharmaceutical levels in patients with some liver diseases [2]. So much so that medical intervention is sometimes necessary to prevent harm [3].
That said, BZDs are not good anti anxiety meds as they actually trigger the brain atrophy which is the physical cause of anxiety (also depression) and inhibit the mechanism by which ADs (also cognitive/behavioural/mindfulness therapies) create the therapeutic response.
Antidepressants have no direct effect on anxiety, or depression in the way say aspirin has on a headache. They work by stimulating the growth of new brain cells (neurogenesis) to replace cells killed, or prevented from growing by high brain stress hormone levels. The therapeutic response is produced by these new cells and the stronger interconnections they forge, not the meds directly. For more detailed explanations see: Depression and the Birth and Death of Brain Cells (PDF) and How antidepressant drugs act.
There is good evidence that BZDs have the same negative impact on hippocampal neurogenesis as stress hormones do and that they can inhibit ADs from working [4]
References:
[1]
Muceniece R, Saleniece K, Krigere L, et al. (2008)
Potato (Solanum tuberosum) juice exerts an anticonvulsant effect in mice through binding to GABA receptors.
Planta Med. 2008 Apr;74(5):491-6. (Abstract)
Kavvadias D, Abou-Mandour AA, Czygan FC, et al (2000)
Identification of benzodiazepines in Artemisia dracunculus and Solanum tuberosum rationalizing their endogenous formation in plant tissue.
Biochem Biophys Res Commun Mar 5;269(1):290-5 (Abstract)
Sand P, Kavvadias D, Feineis D, et al. (2000)
"Naturally occurring benzodiazepines: current status of research and clinical implications."
Eur Arch Psychiatry Clin Neurosci vol 250(4): p 194-202 (Abstract)
Kotz U, (1991)
Occurrence of "natural" benzodiazepines.
Life Sci;48(3):209-15 (Abstract)
Unseld E, Krishna DR, Fischer C, et al (1989)
Detection of desmethyldiazepam and diazepam in brain of different species and plants.
Biochem Pharmacol Aug 1;38(15):2473-8 (Abstract)
[2]
Baraldi M, Avallone R, Corsi L, et al (2000)
Endogenous benzodiazepines.
Therapie Jan-Feb;55(1):143-6 (Abstract)
[3]
Zeneroli ML, Venturini I, Stefanelli S, et al, (1997)
Antibacterial activity of rifaximin reduces the levels of benzodiazepine-like compounds in patients with liver cirrhosis.
Pharmacol Res , Jun;35(6):557-60 (Abstract)
[4]
Boldrini M, Butt TH, Santiago AN, et al. (2014)
Benzodiazepines And The Potential Trophic Effect Of Antidepressants On Dentate Gyrus Cells In Mood Disorders
Int J Neuropsychopharmacol. Dec;17(12):1923-33 (Abstract)
Nochi R, Kaneko J, Okada N, at al. (2013)
Diazepam treatment blocks the elevation of hippocampal activity and the accelerated proliferation of hippocampal neural stem cells after focal cerebral ischemia in mice
J Neurosci Res. 2013 Nov;91(11):1429-39 (Abstract)
Sun Y, Evans J, Russell B, et al [2013]
A benzodiazepine impairs the neurogenic and behavioural effects of fluoxetine in a rodent model of chronic stress
Neuropharmacology. Sep;72:20-8 (Abstract)
Song J, Zhong C, Bonaguidi MA, et al (2012)
Neuronal circuitry mechanism regulating adult quiescent neural stem-cell fate decision.
Nature. Sep 6;489(7414):150-4 (Article | Study full text)
Wu X, Castren E. (2009)
Co-Treatment with Diazepam Prevents the Effects of Fluoxetine on the Proliferation and Survival of Hippocampal Dentate Granule Cells
Biol Psychiatry. Jul 1;66(1):5-8 (Abstract)
Stefovska VG, Uckermann O, Czuczwar M, et al (2008)
Sedative and anticonvulsant drugs suppress postnatal neurogenesis
Ann Neurol. Oct;64(4):434-45 (Abstract)
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The opinions expressed above are based on my observations and, where applicable, interpretation of cited data and are general in nature. Consult your physician before acting on anything stated.