Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917801 (insomnia)
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Zolpidem is a sedative and hypnotic drug belonging to imidazopyridine family. Zolpidem facilitates GABAA function more selectively than benzodiazepines, and produces a selective hypnotic effect. In comparison with benzodiazepines this mechanism could be reduce liability to induce dependence. Recently, some cases of zolpidem abuse and dependence have been published. The Authors report 2 cases of addiction to high dose of zolpidem and compare them with others described in the literature. Both patients had been reknown drug addicts before their first prescription of zolpidem and a borderline personality disorder was diagnosed. The patients rapidly developed over consumption and dependence of the molecule, when taking doses as high as 240 and 400 mg daily. To get zolpidem, one patient falsifies prescriptions. They don't suffer from the sedative effects while searching for anxiolytic and stimulating effects. They were also dysarthric, confused, high energy for mental and physical activity. The cases of zolpidem abuse and dependence in the literature describe these symptoms and others such as losing sense of orientation in time and space, amnesia and visual hallucinations. The most typical withdrawal symptom is high levels of anxiety. Moreover, one patient presents an epileptic seizure whereas the other display a severe psychiatric complication such a psychosis. In the literature, withdrawal was accompanied by confusion, suicidal ideas, nausea, vomiting, sweat, tremors, tachycardia and insomnia rebound. The epileptic seizures are described but acute psychosis complication is rare. Pharmacological hypotheses are described. The effects of zolpidem on GABAA receptor gene expression are consistent with the reduced tolerance liability of this drug as well as with other ability to induce both physical dependence and withdrawal syndrome. Through the review of the literature, the Authors noted that 50% of the cases of dependence on zolpidem are drug addicts, therefore concluding that drug addicts are more likely to become dependent on zolpidem.
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PMID:[Dependence on zolpidem: a report of two cases]. 1510 18

A 43-year-old man with chronic back and shoulder pain was treated with hydrocodone. He began taking excessive amounts of the drug, so his physicians stopped prescribing it. The patient then obtained the muscle relaxant carisoprodol on his own from several sources. He was consuming up to 30 or more tablets/day (> or =10,500 mg/day) for several weeks, then abruptly stopped taking the drug. Within 48 hours he developed anxiety, tremors, muscle twitching, insomnia, auditory and visual hallucinations, and bizarre behavior. The symptoms intensified and peaked on the fourth day after carisoprodol cessation. The patient required brief treatment with olanzapine and tapering dosages of lorazepam while the symptoms gradually resolved. To our knowledge, this is the first documented case of a withdrawal syndrome with carisoprodol. The symptoms most likely resulted because of accumulation of meprobamate, the active metabolite of carisoprodol in humans. Clinicians prescribing carisoprodol should be aware of the possibility for abuse or addiction. Further, we recommend that carisoprodol be designated a controlled substance at the federal level.
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PMID:Carisoprodol withdrawal syndrome. 1558 47

Virtually all psychiatric and substance use disorders are associated with sleep disruption. Studies indicate that psychiatric disorders are related closely to chronic insomnia and that psychoactive substances have acute and chronic effects on sleep architecture. Several aspects of sleep are compromised in individuals taking these substances, ranging from difficulty initiating sleep to difficulty maintaining sleep and hypersomnia. Sleep disturbances are apparent in person taking psychoactive drugs or alcohol and have been found to persist long after withdrawing from these drugs. For some, sleep disturbance can be so severe as to reverse treatment success and precipitate relapse to addiction or dependence. There is increasing evidence that primary insomnia without a concurrent psychiatric disorder is a risk factor for later developing substance use disorders. Patients were asked to complete two brief screening tools, the Michigan Alcohol Screening Test and Drug Abuse Screening Test, to examine substance use patterns among patients referred for a variety of sleep complaints in a sleep disorders clinic. We found that patients who demonstrated a variety of sleep complaints were more likely to have alcohol and drug problems than those in the general populations.
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PMID:Screening for substance use patterns among patients referred for a variety of sleep complaints. 1645 Jun 46

The aim of this article is to summarize the current evidence base about interventions that improve symptoms at the end of life. Moderate to severe symptoms are highly prevalent in the weeks and months before death: 1.4 million individuals have dyspnea; and 1 million have pain. Of those with pain, 300,000 want more pain relief. 700,000 may need more relief, but do not receive it because of the myth of opioid addiction; their physicians do not know how to manage the adverse effects of pain relieving therapies, or they don't know the various options that are available for pain relief. Of the 1 million Americans who die in hospitals, 324,000 had fatigue, 280,000 anorexia, 244,000 dyspnea, 232,000 xerostomia, 208,000 cough, 196,000 pain, 148,000 confusion, 148,000 depression, 140,000 nausea, 92,000 insomnia in 23, and 88,000 vomiting. This is caused in part by clinician ignorance. In a representative sample of oncologists, the most important source of information about symptom control was trial-and-error in practice. In addition, large, well-designed, well-controlled studies of patients at the end of life have not been performed. Clinical practice is guided by extrapolation of data from other populations and from anecdote. The system of care provided by hospice programs in the U.S. provides improved symptom control as compared with hospitals, home health agency, and nursing home systems. Population-based studies of prevalence are needed to gauge outcomes of the implementation of measures to relieve symptoms. Well-powered, definitive studies of both existing and new approaches in terminally ill patients with the most common symptoms are needed. The health care system interventions that are effective in hospice care must be studied so that they can be broadly applied to the care of all dying Americans.
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PMID:Interventions to manage symptoms at the end of life. 1649 73

In studies made in the last decade, patients consulting doctors because of depression and anxiety have very often turned out to suffer from bipolar type II and similar conditions with alternating depression and hypomania/mania (the bipolar spectrum disorders - BP). Specifically, about every second patient seeking consultation because of depression has been shown to suffer from BP, mainly bipolar type II. BP is often concealed by other psychiatric conditions, e.g. recurrent depression, psychosis, anxiety, addiction, personality disorder, attention-deficit hyperactivity disorder and eating disorder. BP shows strong heredity. Relatives of patients with BP also have a high frequency of the psychiatric conditions just mentioned. Conversion ("switching") from recurrent unipolar depressions (recurrent UP) to BP is common in very long longitudinal studies (over decades). Mood-stabilizing medicines are recommended to a great extent in the treatment of BP, since anti-depressive medicines are often not effective and involve a substantial risk of inducing mood swings. Particularly in the long-term pharmacological treatment of depression in BP anti-depressive medicines may worsen the condition, e.g. inducing a symptom triad of dysphoria, irritability and insomnia: ACID (antidepressant-associated chronic irritable dysphoria).
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PMID:Bipolar II and the bipolar spectrum. 1650 Jul 95

Major depression is a mood disorder characterized by a sense of inadequacy, despondency, decreased activity, pessimism, anhedonia and sadness where these symptoms severely disrupt and adversely affect the person's life, sometimes to such an extent that suicide is attempted or results. Antidepressant drugs are not always effective and some have been accused of causing an increased number of suicides particularly in young people. Magnesium deficiency is well known to produce neuropathologies. Only 16% of the magnesium found in whole wheat remains in refined flour, and magnesium has been removed from most drinking water supplies, setting a stage for human magnesium deficiency. Magnesium ions regulate calcium ion flow in neuronal calcium channels, helping to regulate neuronal nitric oxide production. In magnesium deficiency, neuronal requirements for magnesium may not be met, causing neuronal damage which could manifest as depression. Magnesium treatment is hypothesized to be effective in treating major depression resulting from intraneuronal magnesium deficits. These magnesium ion neuronal deficits may be induced by stress hormones, excessive dietary calcium as well as dietary deficiencies of magnesium. Case histories are presented showing rapid recovery (less than 7 days) from major depression using 125-300 mg of magnesium (as glycinate and taurinate) with each meal and at bedtime. Magnesium was found usually effective for treatment of depression in general use. Related and accompanying mental illnesses in these case histories including traumatic brain injury, headache, suicidal ideation, anxiety, irritability, insomnia, postpartum depression, cocaine, alcohol and tobacco abuse, hypersensitivity to calcium, short-term memory loss and IQ loss were also benefited. Dietary deficiencies of magnesium, coupled with excess calcium and stress may cause many cases of other related symptoms including agitation, anxiety, irritability, confusion, asthenia, sleeplessness, headache, delirium, hallucinations and hyperexcitability, with each of these having been previously documented. The possibility that magnesium deficiency is the cause of most major depression and related mental health problems including IQ loss and addiction is enormously important to public health and is recommended for immediate further study. Fortifying refined grain and drinking water with biologically available magnesium to pre-twentieth century levels is recommended.
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PMID:Rapid recovery from major depression using magnesium treatment. 1654 86

Benzodiazepines are relatively well-tolerated medicines but can induce serious problems of addiction and that is why their use is regulated. However, in developing countries like Senegal, these products are used without clear indications on their prescription, their dispensation or their use. This work focuses on the prescription of these medicines with a view to make recommendations for their rational use. Benzodiazepine prescription was studied with psychiatrists or neurologists and generalists in 2003. Specialist doctors work in two Dakar university hospitals and generalists in the 11 health centres in Dakar. We did a survey by direct interview with 29 of 35 specialists and 23 of 25 generalists. All doctors were interviewed in their office. The questionnaire focused on benzodiazepine indications, their pharmacological properties, benzodiazepines prescribed in first intention against a given disease and the level of training in benzodiazepines by doctors. Comparisons between specialists and generalists were made by chi-square test. Benzodiazepines were essentially used for anxiety, insomnia and epilepsy. With these diseases, the most benzodiazepines prescribed are prazepam against anxiety and insomnia and diazepam against epilepsy. About 10% of doctors do not know that there is a limitation for the period of benzodiazepine use. The principal reasons of drugs choice are knowledge of the drugs, habit and low side effects of drugs. All generalists (100%) said that their training on benzodiazepines is poor vs. 62.1% of specialists, and doctors suggest seminars, journals adhesions and conferences to complete their training in this field. There are not many differences between specialists and generalists except the fact that specialists prefer prazepam in first intention in the insomnia treatment where generalists choose bromazepam. In addition, our survey showed that specialists' training in benzodiazepines is better than that of generalists. Overall, benzodiazepine prescription poses problems particularly in training, and national authorities must take urgent measures for rational use of these drugs.
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PMID:Benzodiazepines prescription in Dakar: a study about prescribing habits and knowledge in general practitioners, neurologists and psychiatrists. 1667 57

There is convincing evidence that acupuncture (AP) is effective for the treatment of postoperative and chemotherapy-induced nausea/vomiting, as well as postoperative dental pain. Less convincing data support AP's efficacy for chronic pain conditions, including headache, fibromyalgia and low back pain. There is no evidence that AP is effective in treating addiction, insomnia, obesity, asthma or stroke deficits. AP seems to be efficacious for alleviating experimental pain by increasing pain thresholds in human subjects and it appears to activate analgesic brain mechanisms through the release of neurohumoral factors, some of which can be inhibited by the opioid antagonist naloxone. In contrast to placebo analgesia, AP-related pain relief takes some time to develop and to resolve. Furthermore, repetitive use of AP analgesia can result in tolerance that demonstrates cross-tolerance with morphine. However, it appears that not all forms of AP are equally effective for providing analgesia. In particular, electro-AP seems to best deliver stimuli that activate powerful opioid and nonopioid analgesic mechanisms. Thus, future carefully controlled clinical trials using adequate electro-AP may be able to provide the necessary evidence for relevant analgesia in chronic pain conditions, such as headache, fibromyalgia, irritable bowel syndrome and low back pain.
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PMID:Mechanisms of acupuncture analgesia for clinical and experimental pain. 1673 14

Insomnia is one of the most common complaints faced in clinical practice. The limited pharmacological options available make the treatment of this complaint a challenge. All of the available benzodiazepines and non-benzodiazepine hypnotics have the potential to induce addiction, cause withdrawal symptoms, or trigger rebound insomnia. Further, the evidence supporting the utility of commonly prescribed options such as antidepressants and antipsychotics is limited. Melatonin is a hormone that has been associated with soporific effects. Based on this premise, a melatonin receptor agonist was created. Ramelteon was approved by the Food and Drug Administration in 2005 and is the only medication indicated for the long-term treatment of insomnia. A critical review with a clinical perspective of randomized, placebo-controlled clinical trials was conducted to determine the efficacy of melatonin and ramelteon for the treatment of insomnia. Based on this review, it appears that more placebo-controlled trials are indicated before valid judgments concerning the efficacy of both melatonin and ramelteon can be made. In the meantime, there is some support for the use of melatonin for the treatment of insomnia, and findings concerning ramelteon also appear promising. Nevertheless, clinicians who prescribe melatonin or ramelteon should be cautious and carefully monitor both potential benefits and adverse effects, since data on melatonin are based on studies with multiple limitations and only three controlled trials have been done with ramelteon.
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PMID:Searching for new options for treating insomnia: are melatonin and ramelteon beneficial? 1688 48

Chronic pain, whether arising from viscera, bone, or any other tissue or structure, is, more often than commonly thought, the result of a mixture of pain mechanisms, and therefore there is no simple formula available to manage chronic complex pain states. Box 1 summarizes a pharmacological algorithm for difficult-to-treat chronic pain, which merely introduces the medication aspect of the treatment. In effect, any comprehensive algorithm should call for an interdisciplinary approach that would include rehabilitation, as well as psychosocial, and when indicated, interventional techniques. Box 1 Analgesic algorithm for difficult-to-treat pain syndromes. Pharmacological Interventions. Moderate to severe pain/functional impairment; pain with a score of >4 on the brief pain inventory. 1. Gabapentinoid (gabapentin, pregabalin)+/-Opioid/opioid rotation or 2. Antidepressant (TCA, duloxetine, venlafaxine)+/-Opioid/opioid rotation or 3. Gabapentinoid+antidepressant+Opioid/opioid rotation; in addition, may consider trials of one or more of the following adjuvants when clinically appropriate: Topical therapies for cutaneous allodynia/hyperalgesia. Anti-inflammatory drugs (corticosteroids for acute inflammatory neuropathic pain)IV bisphosphonates for cancer bone pain or CRPS/RSDNon-gabapentinoid AEDs such as carbamazepine or oxcarbazepine or lamotrigine+/-baclofen for intermittent lancinating pain due to cranial neuralgiasNMDA antagonists Mexiletine On a compassionate basis, according to the patient's clinical condition and pain mechanism, the physician may want to consider an empirical trial of one or more of the emergent topical, oral or parenteral/intrathecal therapies as discussed in the text. If SMP, consider topical clonidine and sympatholytic interventions; if clinically feasible, trials of topical therapies, eg, lidocaine 5% patch, may be considered for a variety of pain states and features.The major rationale for introducing adjuvants is to better balance efficacy and adverse effects. The following scenarios should prompt the use of adjuvants in clinical practice: The toxic limit of a primary analgesic has been reached. The therapeutic benefit of a primary analgesic has plateaued, eg, treatment has reached its true efficacy limit or pharmachodynamic tolerance has developed. The primary analgesic is contraindicated, eg, substance abuse, aberrant behavior, organ failure, allergy, and so forth. Subjective and qualitative symptoms demand broader coverage. Patients often convey that different medications will impart distinct analgesic benefits. Presence of disabling nonpainful complaints and need to manage symptoms such as insomnia, depression, anxiety, and fatigue that all cause worsening of the patient's quality of life and function. Physicians have also been drawn to the adjuvants secondary to new realities of clinical practice. Moreover, aversion to addiction and diversion remains a potent force that shapes prescribing profiles.
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PMID:Adjuvant analgesics. 1716 7


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