Though rare, extreme hypothyroidism can be potentially fatal. Benzodiazepine-class drugs like Klonopin clonazepam have only minor interference with thyroid function per the Clinical Neuropharmacology journal in though hypothyroidism may affect benzodiazepine use. This is important for several reasons including the following:. The evidence suggests that thyroid disorders do not directly lead to clonazepam abuse, but its symptoms may motivate substance use that indirectly leads to addiction.
Similarly hypothyroidism can potentially motivate other forms of substance abuse including the following:. According to the Mayo Clinic , the overproduction of thyroid hormones can potentially cause a rapid heartbeat, hand tremors, anxiety, sweating, heat sensitivity, fatigue, insomnia, frequent bowel movements, thinning skin and brittle hair. A person might attempt to self-medicate these symptoms with the same substances but for different reasons including the following:.
Furthermore the impact of thyroid disorders on mental health cannot be discounted. Depression and anxiety are common symptoms of both hyperthyroidism and hypothyroidism, and co-occurring mood disorders are a significant risk factor for addiction. Several studies demonstrate the connection between mental health and addiction including the following:. Coincidentally the New York Times noted in that the mental health medication lithium can induce hypothyroidism, which means mental health disorders can also precede thyroid problems.
If an addiction does occur, professional treatment is the best recovery option regardless of what initiated the original substance use. Rehabilitation centers strive to treat the whole person, which includes coordinating treatment for thyroid and mental health disorders like addiction to clonazepam. Potential services provided during treatment can include the following:. Just as follow-up sessions are needed to check the thyroid disorder, aftercare services are strongly encouraged for addiction and mental health care.
Furthermore, bradycardia associated with clonazepam is rare. To date, two cases of arrhythmia related to clonazepam have been reported in the literature 5 , 6. One case was a four-year-old boy presenting with an atrioventricular block associated with the excessive administration of clonazepam 5. The other case was a year-old man with end-stage renal disease who presented with sinus bradycardia caused by the interaction of amiodarone and clonazepam; the patient also had a medical history of sinus bradycardia related to diazepam 6.
Although the exact mechanisms are unknown, clonazepam may have caused sinus bradycardia by blocking the T-type calcium channels, which contribute to the automaticity of the sinoatrial and atrioventricular nodes 7 , 8. Benzodiazepine receptors consist of central- and peripheral-type receptors 9. Peripheral-type benzodiazepine receptors, which are distributed to the peripheral tissues, including the cardiovascular system, have various functions, such as the regulation of voltage-dependent calcium channels Benzodiazepine receptors are also divided into high-affinity and low-affinity receptors; the former selectively bind in nanomolar concentrations of benzodiazepines, and the latter bind in micromolar concentrations and regulate voltage-sensitive calcium channels 11 , Clonazepam has been referred to as a specific agonist for the central-type receptor in contrast to diazepam, which is a non-specific agonist for both central- and peripheral-type receptors 7.
Clonazepam may therefore antagonize calcium channels despite the specific ligand for central-type benzodiazepine receptors. The long-term administration of clonazepam in elderly patients with multiple comorbidities may lead to an overdosage and adverse drug events. Clonazepam is mainly metabolized in the liver, primarily by cytochrome P isoenzyme 3A4 4 , In the present case, not only age-related decreases in the liver size, hepatic blood flow, and liver cytochrome P activity, but also complicated liver dysfunction due to chronic cholecystitis and total parenteral nutrition-induced fatty liver may have been associated with the decreased hepatic drug clearance of clonazepam.
In addition, the cytochrome P levels and activities are reduced during infections and inflammation by up-regulated cytokines, such as interleukin 6 With aging, the amount of body fat increases and the total body water decreases. Lipid-soluble drugs have an increased distribution volume in the elderly; therefore, drug accumulation and prolongation of the elimination half-life may occur with long-term administration Age-dependent decreases in the serum albumin concentration influence the drug protein binding potency, and increases in the free concentration of highly protein-bound drugs may cause toxicity in patients with hypoalbuminemia In addition, complicated subclinical hypothyroidism, likely caused by aging, may contribute to bradyarrhythmia.
Several limitations associated with the present study warrant mention. First, the serum clonazepam level at bradycardia onset was within the therapeutic range; however, we nevertheless considered the possibility of clonazepam-associated bradycardia because the condition disappeared after the drug was stopped. In a previous report, neither the therapeutic nor the side effects of clonazepam were clearly correlated with its serum concentration 1.
For example, the serum clonazepam level was elevated to toxic levels in one case of clonazepam-associated atrioventricular block but not elevated in a case of clonazepam-associated sinus bradycardia 5 , 6. Furthermore, advanced age is associated with an increased sensitivity to benzodiazepines, including clonazepam 15 , Thus, clonazepam-associated adverse events may occur even if the levels are within the normal range.
If possible, the dose of clonazepam should be reduced to prevent adverse effects in elderly patients. Second, we did not examine the patient for ischemic heart disease. Considering the findings on her electrocardiograms, ischemic heart disease might have been concealed. An ischemic heart attack may have influenced the occurrence of bradycardia. A retrospective consecutive study of heart necropsy results reported severe coronary atherosclerosis in 8. In addition, sinoatrial node dysfunction is often attributed to cardiac ischemia and idiopathic age-related fibrosis However, we suspect that, in this elderly disabled woman, a thorough examination using coronary angiography may not have improved her prognosis.
Third, cardiac conduction disturbances may also have been concealed in the present case. A previous electrocardiogram demonstrated multiple P wave contours, which may suggest sick sinus syndrome. Furthermore, ectopic atrial rhythm, sinoatrial block, and paroxysmal atrial fibrillation were observed after the cessation of clonazepam. Aging is associated with progressive fibrosis in both the sinoatrial node and atrioventricular conduction systems 18 , Previously concealed sinoatrial and atrioventricular conduction disturbance might have become apparent in the present patient through the action of clonazepam.
Fourth, a chronic inflammatory state associated with gallstones and renal stones may have induced a transient fever and influenced the recovery of the patient's pulse rate. However, only the discontinuation of clonazepam clearly improved the severe bradycardia; the adverse effects of clonazepam may therefore have been a major cause of bradycardia.
In disabled elderly individuals with multiple comorbidities, it may be difficult to fully elucidate their complicated pathophysiology affected by various clinical factors in an integrated manner. Benzodiazepines, including clonazepam, may cause severe bradycardia. Benzodiazepines may have calcium channel-blocking properties, which may explain the observed bradyarrhythmia.
It is important for clinicians to be aware of benzodiazepine-associated bradycardia in order to prevent elderly patients from experiencing adverse drug events. National Center for Biotechnology Information , U. Journal List Intern Med v. Published online Aug Received Sep 7; Accepted Jan To view the details of this license, please visit https: Abstract We herein report an year-old woman who was taking clonazepam at 1.
Introduction Clonazepam, a benzodiazepine derivative, is frequently used in a variety of clinical situations, such as to treat epilepsy, anxiety, and myoclonus, even in elderly patients 1 - 3. Case Report An year-old woman was admitted to the geriatric long-term care ward of our hospital with an old cerebral infarction complicated with symptomatic epilepsy. Electrocardiogram at the onset of severe bradycardia recorded 4 h after the last intake of clonazepam 0.
Electrocardiogram recorded 22 months before the occurrence of bradycardia. The presence of multiple P wave contours may suggest sick sinus syndrome. Poor R wave progression in leads V is also observed. Time-course of electrocardiogram changes. Bradycardia disappeared on day 3 C. However, ectopic atrial rhythm C, D, Discussion In this patient, discontinuing clonazepam improved the severe bradyarrhythmia, and we made a diagnosis of clonazepam-associated bradycardia.
Pharmacological treatment of social anxiety disorder. Mod Trends Pharmacopsychiatri Levy A, Chen R. Curr Treat Options Neurol Antiepileptic drugs-best practice guidelines for therapeutic drug monitoring: