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Insomnia drugs and impaired driving ability
posted Friday, 27 March 2009
Julie Johansen
A new study from the Norwegian Institute of Public Health shows a positive link between the amount of the hypnotic zopiclone (Imovane®, Lunesta®, Zimovane®) in the blood and the chance of being assessed as impaired in a clinical examination. The study also included drivers who only showed alcohol in their blood test.
"This could be important information in the discussion about establishing legal limits in traffic for sedatives or sleep-inducing medicines as we have for alcohol," says Ingebjørg Gustavsen from the Division for Forensic Toxicology and Drug Research.
Hypnotics that contain zopiclone and zolpidem (Ambien®, Damixan®, Stilnox®) are widely used throughout the world and it is reported that between 3 and 7 percent of the adult population uses these drugs. Researchers at the Norwegian Institute of Public Health studied if there is a link between the concentration of zopiclone or zolpidem in the blood and being assessed as impaired during a clinical examination. The study was done on anonymised material by comparing blood samples and results from clinical tests for the period January 2000 to December 2007. The same study was performed on another group of drivers who only had alcohol in the blood.
The proportion of drivers who were evaluated as impaired increased with zopiclone-concentration in the blood. A similar positive link was not found for zolpidem. For alcohol, as expected, there was a significant link between the proportion of impaired drivers and alcohol concentration in the blood.
"We know that the clinical examination performed on suspicion of driving under the influence is a test that is most sensitive for alcohol impairment, and less sensitive for other substances. Other types of impairment are therefore not necessarily picked up with this study, which can explain why we have not found positive links for zolpidem. Another reason can be that there were few drivers in our sample, particularly in the groups with low concentrations," says Gustavsen.
The proportion of drivers who were evaluated as impaired was relatively similar for the group that had 130 µg/l zopiclone or more in the blood and the group that had a blood alcohol concentration higher than 0.1 percent. A concentration of 130 µg/l zopiclone in the blood suggests intake of at least 2 large doses of zopiclone.
"Zopiclone and zolpidem are usually used in moderate amounts before bedtime, and will often be excreted from the body by the next morning. There are few users of these hypnotics that are stopped by police based on suspicion of driving under the influence. In the meantime we know that these substances also have abuse potential, as do other sedative or sleep-inducing medicines. Over 90 % of the drivers included in the study because of zopiclone- / zolpidem-use had higher concentrations of the substances in the blood than one would expect from normal therapeutic use of sleeping tablets before bedtime," concludes Gustavsen.
Gustavsen I, Al-Sammurraie M, Mørland J, Bramness JG. Impairment related to blood drug concentrations of zopiclone and zolpidem compared to alcohol in apprehended drivers. Accid Anal Prev. 2009 Mar; doi:10.1016/j.aap.2009.01.011 [Abstract]
Comment:
While this study didn't find significant impairment with zolpidem, this hypnotic has been linked to sleep walking, sleep driving and other potentially dangerous behavior. However, it is also one of the few sleeping pills approved (
) - with restrictions - by the USAF for use by air crew.
While this study didn't find significant impairment with zolpidem, this hypnotic has been linked to sleep walking, sleep driving and other potentially dangerous behavior. However, it is also one of the few sleeping pills approved (
) - with restrictions - by the USAF for use by air crew. comments
Action-potential
Wave of electrochemical activity generated by the flow of positively charged ions across the neuronal membrane which causes a neuron to 'fire'- Click page link for more information -
Affective disorders
Mental disorders characterized by dramatic changes or extremes of mood - depression, mania, or both - including depression, bipolar disorder (manic depression), and schizo affective disorders.- Click page link for more information -
Alleles
An alternative form of a gene (one member of a pair) that is located at a specific position on a specific chromosome.- Click page link for more information -
Amygdalae
Two almond-shaped groups of neurons - there is one amygdala (Greek for almond) in each brain hemisphere. They have the primary role in processing and storing memories of emotional reactions.Part of the Limbic System the amygdalae trigger an instant fear reaction to perceived threats, real or imagined.
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Anterior cingulate cortex
Involved in empathy, emotions, cognitive control (attention, conflict monitoring during information processing) and plays a role in stimulus reinforcement learning and reward-guided selection of actions.Also controls autonomic functions such as heart rate and blood pressure in the context of current behavior.
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Arousal of the autonomic nervous system which regulates many bodily functions and produces the physical symptoms of stress including the 'fight-or-flight' response.Brain-derived neurotrophic factor
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A polypeptide hormone and neuro- transmitter involved in the stress response.CRF hyper secretion is believed to contribute to hyperactivity of the hypothalamic-pituitary-adrenal axis in depressed patients. Hyper secretion has also been implicated in anxiety.
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Epidemiological studies describing population characteristics which collect data at one point in time and then consider relationships between observed characteristics.. Because they don't look at time trends they cannot establish causes.
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A parent, sibling or child of an individual.Gamma-Aminobutyric Acid (GABA)
The major inhibitory neurotransmitter of the central nervous system. Dampens brain activity and promotes a state of calm.An amino acid produced in the brain as a by-product of the Krebs glucose metabolism cycle which powers brain cells.
Note 1: Benzodiazepines (Valium® etc) do not increase brain GABA levels, but increase the sensitivity of GABA receptors.
Note 2: GABA does not normally penetrate the Brain-Blood-Barrier (the BBB tends to pull GABA from the brain into the blood stream (Kakee A, 2001)) so GABA supplements are, at best, expensive placebos.
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Support cells in the brain and spinal cord which provide physical and nutritional support for neurons, form the blood-brain barrier, clear dead cells and other debris, insulate neurons and, as part of the immune system, protect the brain from microorganisms.Long thought not to conduct electrical impulses as the neurons do, there is growing evidence that they do modulate neurotransmission.
The largest group of cells of the central nervous system being between 50-100 times more abundant than neurons.
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Haplotype
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Because genes are either dominant or recessive, the genetic makeup (genotype) of an organism cannot always be determined by physical appearance alone.
Hippocampus
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Anatomical structures that perform the same function in different biological species having evolved from the same structure in a shared ancestor species.Hypothalamus
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Signaling molecules critical to the functioning of the immune system.A recombinant form of IL-2 has been approved as an anti cancer drug and and may have anti viral properties. Changes in mental states including irritability, confusion, or depression are a known side-effect.
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Brain structure of the 'old' mammalian brain comprising the hippocampus, amygdalae, anterior thalamic nuclei, and the diencephalon in the forebrain. Regulates memory, and the emotions including fear, anger, and of sexual behavior.- Click page link for more information -
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A molecule that is able to bind to and form a complex with a biomolecule to serve a biological purpose. Neurotransmitters are one type of ligand.Longitudinal study
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Mathematical technique to amalgamating, summarizing, and reviewing previous quantitative research to arrive at one overall measure of treatment effect.A weakness of the method is that sources of bias in the original research are not controlled by the method. A good meta-analysis of badly designed studies will still result in bad statistics.
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Mindfulness
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Mindfulness meditation/ psychotherapy
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Narrative Exposure Therapy
Therapy developed to treat PTSD. Based on cognitive behavioral exposure therapy, it adapts classical exposure therapy to meet needs of traumatized survivors of war and torture.Survivors are asked to describe what happened to them in great detail, focusing on what they saw, heard, smelt, etc, and their feelings and thoughts at the time. Initially, sessions are distressing, but as they are long enough to allow habituation, distress levels diminish towards the end and more and more details are recalled.
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Neurogenesis
Process by which new neurons are generated after the postnatal stage of development. It appears to only occur in two areas of the brain, the hippocampus and the olfactory bulbs. Hippocampal neurogenesis is thought to counter anxiety and depression.- Click page link for more information -
Neuropeptide
One of about 100 peptides including endorphins, enkephalins, oxytocin and vasopressin which mediate brain function by regulating gene expression, local blood flow and synaptogenesis. The neuropeptides Cholecystokinin, Substance P and Neuropeptide Y have been linked to anxiety and depressive disorders.- Click page link for more information -
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The brain's ability to reorganize itself by forming new neural connections.- Click page link for more information -
Nucleus accumbens
Twin brain structures (one in each hemisphere) involved in reward, laughter, pleasure, addiction, fear, and the placebo effect.- Click page link for more information -
Polymorphism
Natural variations in a gene, DNA sequence, protein, or chromosome.-Click page link for more information-
Prefrontal Cortex
Area of the brain's frontal lobes involved in planning complex cognitive behaviors, the expression of personality and social behavior.- Click page link for more information -
Prospective study
Tests a specific question, usually about how a specific exposure(s) affects a specific outcome(s) by recruiting appropriate participants and checks the outcomes over the following months or years.Psychodynamic psychotherapy
Talking therapy used to help a person find relief from emotional pain. It is based on the theories and techniques of Freudian/Jung style psychoanalysis. However, practitioners don't necessarily accept the 'classical' psychoanalysis theory that emotional conflicts are primarily sexual in nature.Receptor
Short-lived protein molecules embedded in the cell wall of neurons, especially of their synapses, to which neurotransmitters attach to initiate an action. Also called ´binding sites´- Click page link for more information -
Receptor agonist
A chemical which is able to bind to receptors of a neurotransmitter and trigger the same biological response as that neurotransmitter.Receptor antagonist
A drug that is so similar chemically to a neurotransmitter that it is capable of binding to a receptor for the neurotransmitter but which does not trigger the biological response of that neurotransmitter. By blocking its receptors the antagonist disrupts or inhibits the action of the neurotransmitter.Retrospective study
Research using data on exposures and/or outcomes that have already been collected through medical records or as part of another study. Such data may not be as reliable as data collected prospectively, as it relies on the accuracy of records made at the time, and on people’s recall of past events, which can be inaccurate (referred to as recall bias).Safety behavior
Behavior undertaken to reduce anxious thoughts, or to keep yourself 'safe' from imagined threats, or to hide your anxious state from others. Examples include constant monitoring of breathing or heart rate, shopping during quiet retail hours, taking precautionary tranquillizers "just in case," taking circuitous routes to avoid highways or bridges when driving, sitting close to exits, avoiding eye contact, playing with keys to hide trembling hands.Seasonal affective disorder
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Serotonin syndrome
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Serotonin transporter
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Manifests as chronic, persistent complaints of varied physical symptoms that have no identifiable organic origin or basis. Often co morbid with other psychological disorders, particularly anxiety or mood disorders, plus irritable bowel syndrome and chronic pain. Occurs in 0.2% to 2% of females and 0.2% of males. Also known as Briquet's disorder.Sympathetic nervous system
The part of the nervous system which controls the body’s internal, involuntary processes including breathing, digestion, blood vessel tone, heart rate, etc. It also mediates the fight-or-flight response.Subgenual cingulate
Brain region high in serotonin transporter-binding sites, with strong projections to the hypothalamus and brain stem. Modulates autonomic/neuroendocrine responses and neurotransmitter transmission during the neural processing of reward, fear, and stress. May be critical for modulating widespread behavioral changes mediated by the cortex. Volume is often decreased in mood disorders patients.Also known as Brodmann area 25.
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Synapses
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Thalamus
Regulates sleep and awake states, arousal and awareness. Processes and relays sensory information to the cerebral cortex where they are experienced as sensations of pain, touch, or temperature. Damage to the thalamus can produce permanent coma.- Click page link for more information -
Tumor necrosis factor-α
A cytokine which has wide range of pro inflammatory actions and induce necrosis (death) of tumor cells. Exacerbates chronic inflammatory autoimmune diseases such as rheumatoid arthritis.Blood plasma levels are raised in patients with depression. Research had shown that antidepressants reduce its expression.
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White matter
Regions of the brain and spinal cord largely composed of nerve fibers (axons) sheathed in insulating myelin composed of lipids (fats) which give them their color.White matter abnormalities (hyperintensities):
Damage to the myelin insulation. May be inherited, the result of disease (Multiple Sclerosis) or physical injury, stroke etc. Most brains accumulate some WM abnormalities with age.
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