{"id":602,"date":"2020-02-17T20:21:25","date_gmt":"2020-02-17T14:51:25","guid":{"rendered":"https:\/\/medicineplexus.com\/?p=602"},"modified":"2020-02-17T20:21:25","modified_gmt":"2020-02-17T14:51:25","slug":"pharmacotherapy-of-sleep-disorders","status":"publish","type":"post","link":"https:\/\/medicineplexus.com\/pharmacotherapy-of-sleep-disorders\/","title":{"rendered":"Pharmacotherapy of Sleep Disorders"},"content":{"rendered":"\n<p><strong>Pharmacotherapy of Sleep Disorders<\/strong><\/p>\n\n\n\n<ul><li>Sleep is a reversible behavioral state of perceptual&nbsp; disengagement from and unresponsiveness to the environment<\/li><li>It constitutes a complex amalgam of physiologic and behavioral processes<\/li><\/ul>\n\n\n\n<p><strong>It is typically accompanied by<\/strong><\/p>\n\n\n\n<ul><li>Postural recumbence<\/li><li>Behavioral quiescence<\/li><li>Eye closure<\/li><\/ul>\n\n\n\n<p><strong>Problem statement<\/strong><\/p>\n\n\n\n<ul><li>17 hours of sustained wakefulness &nbsp;<strong>blood alcohol level of 0.05%<\/strong><\/li><li>Associated with <strong>accidents and human errors<\/strong><\/li><li><strong>10\u201315% of fatal motor-vehicle crashes<\/strong> occur due to sleepiness or driver fatigue<\/li><li><strong>Night time use of TV, mobile phones <\/strong><strong>\u00e0 Sleep problems<\/strong> <strong>&nbsp;<\/strong><\/li><li><strong>Cognitive impairment<\/strong> seen with sleep disorders<\/li><li>Associated with short and long-term effects on health and well-being and <strong>quality of life<\/strong><\/li><\/ul>\n\n\n\n<ul><li><strong>Sleep \u00e0 <\/strong>NREM and REM type \u00e0 Sleep cycle<\/li><\/ul>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"654\" height=\"275\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-191.png?w=654\" alt=\"\" class=\"wp-image-603\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-191.png 654w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-191-300x126.png 300w\" sizes=\"(max-width: 654px) 100vw, 654px\" \/><\/figure>\n\n\n\n<ul><li><strong>waking state<\/strong> \u00e0 eyes open \u00e0 high-frequency (15\u201360 Hz), low-amplitude activity (~30 \u03bcV) activity \u00e0 <strong>beta activity<\/strong><\/li><li><strong>Descent into stage I non- REM sleep<\/strong> \u00e0 decreasing EEG frequency (4\u20138 Hz) and increasing amplitude (50\u2013100 \u03bcV) \u00e0 <strong>theta waves<\/strong><\/li><li><strong>Descent into stage II non-REM sleep<\/strong> \u00e0 by 10\u201315 Hz oscillations (50\u2013150 \u03bcV) called <strong>spindles,<\/strong> which <strong>occur periodically<\/strong> and last for a few seconds<\/li><li><strong>Stage III non-REM sleep<\/strong> \u00e0 slower waves at <strong>2\u20134 Hz<\/strong> (100\u2013150 \u03bcV)<\/li><li><strong>Stage IV sleep<\/strong> is defined by <strong>slow waves <\/strong><strong>\u00e0 delta waves<\/strong> at 0.5\u20132 Hz (100\u2013 200 \u03bcV)<\/li><li><strong>REM sleep<\/strong> &nbsp;\u00e0 low-voltage, high-frequency activity similar to the EEG activity of individuals who are awake<\/li><li>Each <strong>sleep cycle<\/strong> lasts for about <strong>90 mins.<\/strong> <strong>Max time about 40-50% spent in phase II<\/strong>. REM sleep 20-25 %, <strong>Most prominent phase is the slow wave sleep (Stage IV).<\/strong> Duration of REM sleep increases as one grows up.<\/li><\/ul>\n\n\n\n<ul><li><strong>five neurotransmitters :<\/strong> <strong>histamine, dopamine, norepinephrine, serotonin, and acetylcholine<\/strong> \u00e0 ascending reticular activating system, because they are known to work together to regulate arousal<\/li><\/ul>\n\n\n\n<p><strong>Insomnia<\/strong><\/p>\n\n\n\n<ul><li>defined in ICSD-3 as a complaint of <strong>trouble initiating or maintaining sleep which is associated with day-time consequences and is not attributable to environmental circumstances<\/strong> or inadequate opportunity to sleep<\/li><li>The disorder is identified as <strong>chronic<\/strong> when it has <strong>persisted for at least three months<\/strong> at a frequency of at least three times per week.<\/li><li>DSM-V: 3 nights\/week; 1 months but &lt; 3 months: episodic, &gt;3 months persistent insomnia<\/li><li>Insomnia is a <strong>more prevalent<\/strong> <strong>\u00e0 females<\/strong> than among males, with a gender ratio of about 1.44:1.<\/li><\/ul>\n\n\n\n<ul><li>Insomnia is a common comorbidity of many medical conditions, including diabetes, coronary heart disease, chronic obstructive pulmonary disease, arthritis, fibromyalgia, and other chronic pain conditions. The <strong>risk relationship appears to be bidirectional: insomnia increases the risk of medical conditions, and medical problems increase the risk of insomnia<\/strong>.<\/li><\/ul>\n\n\n\n<ul><li><strong>Diagnosis <\/strong><strong>\u00e0 Polysomnography<\/strong> usually shows impairments of sleep continuity Eg: increased sleep latency, decreased stages 3 and 4 sleep<\/li><\/ul>\n\n\n\n<p><strong>General treatment measures<\/strong><\/p>\n\n\n\n<ul><li>Treatment of comorbid medical and psychiatric conditions<ul><li>Modifying sleep interfering medications<\/li><\/ul><ul><li>Optimizing the sleep environment<\/li><\/ul><\/li><\/ul>\n\n\n\n<p><strong>Specific treatment of insomnia<\/strong><\/p>\n\n\n\n<ul><li>Cognitive Behavioral Therapy (CBT)<\/li><li>Pharmacotherapy<\/li><li><strong>Indian psychiatry guidelines:<\/strong> For the short-term insomnia, pharmacotherapy is indicated, while for the chronic insomnia, cognitive behavior therapy for insomnia (CBT-I) is preferred.<\/li><\/ul>\n\n\n\n<p><strong>CBT-I<\/strong><\/p>\n\n\n\n<ul><li>Education regrading sleep physiology and sleep hygiene<\/li><li>Addressing dysfunctional beliefs<\/li><li>Stimulus control therapy<\/li><li>Sleep restriction<\/li><li>Relaxation training<\/li><li>Maintaining sleep diary to monitor therapy<\/li><\/ul>\n\n\n\n<p><strong>Pharmacotherapy of insomnia<\/strong><\/p>\n\n\n\n<p><strong>First line therapy<\/strong><\/p>\n\n\n\n<ul><li>Short\/intermediate acting benzodiazepines or newer BZD receptor agonistic modulators [BzRAs] or Ramelteon<\/li><\/ul>\n\n\n\n<p><strong>Second line therapy<\/strong><\/p>\n\n\n\n<ul><li>Other drugs, such as sedating antidepressants or anticonvulsant medications particularly when comorbidities (e.g. mood disorder or epilepsy) are present<\/li><\/ul>\n\n\n\n<p><strong>Benzodiazepines<\/strong><\/p>\n\n\n\n<ul><li>The lack of direct channel activation by benzodiazepines and their dependence on the presynaptic release of GABA at the GABAA receptor likely contribute to the safety of these agents as compared to barbiturates.<\/li><\/ul>\n\n\n\n<figure class=\"wp-block-image size-large is-resized\"><img loading=\"lazy\" decoding=\"async\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-192.png?w=360\" alt=\"\" class=\"wp-image-604\" width=\"359\" height=\"269\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-192.png 360w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-192-300x225.png 300w\" sizes=\"(max-width: 359px) 100vw, 359px\" \/><\/figure>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"357\" height=\"240\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-193.png?w=357\" alt=\"\" class=\"wp-image-605\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-193.png 357w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-193-300x202.png 300w\" sizes=\"(max-width: 357px) 100vw, 357px\" \/><\/figure>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"360\" height=\"232\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-194.png?w=360\" alt=\"\" class=\"wp-image-606\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-194.png 360w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-194-300x193.png 300w\" sizes=\"(max-width: 360px) 100vw, 360px\" \/><\/figure>\n\n\n\n<ul><li>Z drugs do not disturb the sleep architecture<\/li><\/ul>\n\n\n\n<ul><li>Despite the shortening of durations of stage 4 and REM sleep, benzodiazepine administration typically increases total sleep time, largely by increasing the time spent in stage 2, which is the major fraction of non-REM sleep. Decrease REM sleep time but increase the number of cycles<\/li><\/ul>\n\n\n\n<ul><li>Chronic benzodiazepine use poses a risk for development of dependence and abuse<\/li><li>Tolerance has been observed with all currently licensed hypnotics with the exception of melatonin<\/li><li>If used for more than 3 weeks, withdraw slowly<\/li><li>Overdose: Flumazenil<\/li><\/ul>\n\n\n\n<p><strong>Melatonergic drugs<\/strong><\/p>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"327\" height=\"305\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-195.png?w=327\" alt=\"\" class=\"wp-image-607\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-195.png 327w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-195-300x280.png 300w\" sizes=\"(max-width: 327px) 100vw, 327px\" \/><\/figure>\n\n\n\n<ul><li>Endogenous melatonin \u00e0 secreted by the pineal gland<\/li><li>mainly acts in the suprachiasmatic nucleus to regulate circadian rhythms.<\/li><li>three types \u00e0 melatonin 1 and 2 (MT1 and MT2), which are both involved in sleep, and<\/li><li>melatonin 3 \u00e0 not thought to be involved in sleep physiology.<\/li><\/ul>\n\n\n\n<ul><li><strong>Ramelteon<\/strong> is efficacious in combating both transient and chronic insomnia, with no tolerance occurring in its reduction of sleep onset latency even after 6 months of drug administration<\/li><\/ul>\n\n\n\n<ul><li><strong>Agomelatine<\/strong> withdrawn from&nbsp; due to US due to hepatic impairment<\/li><li>Agomelatine is not only an MT1 and MT2 receptor agonist, but is also a 5HT2C and 5HT2B receptor antagonist and is available as an antidepressant in Europe<\/li><\/ul>\n\n\n\n<p><strong>Tricyclic antidepressants<\/strong><\/p>\n\n\n\n<ul><li><strong>Doxepin<\/strong><\/li><li>at antidepressant doses (150\u2013300 mg\/day), inhibits serotonin and norepinephrine reuptake and is an antagonist at histamine 1, muscarinic 1, and \u03b11-adrenergic receptors.<\/li><li><strong>At low doses<\/strong> (1\u20136 mg\/day), however, <strong>doxepin is quite selective for histamine 1 receptors<\/strong> and thus may be <strong>used as a hypnotic.<\/strong><\/li><li>taken in initial doses of 6 mg (3 mg in the elderly) within 30 min of bedtime<\/li><li><strong>Approved by the FDA in 2010 for the treatment of sleep maintenance insomnia.<\/strong><\/li><li>ADRs: Abnormal thinking and behavior have been observed following its use, and it can worsen suicidal ideation and depression.<\/li><\/ul>\n\n\n\n<p><strong>Orexin antagonists <\/strong><strong>\u00e0 <\/strong><strong>Suvorexant<\/strong><\/p>\n\n\n\n<ul><li>neurotransmitter orexin (also called hypocretin) is made by cells located in the hypothalamus<\/li><li>Approved by US FDA in 2014<\/li><li>Not available in india<\/li><li>s\/e \u00e0 Daytime somnolence, Possibility of the worsening of depression or suicidal ideation<\/li><\/ul>\n\n\n\n<p><strong>Off label drugs<\/strong><\/p>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"351\" height=\"195\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-196.png?w=351\" alt=\"\" class=\"wp-image-608\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-196.png 351w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-196-300x167.png 300w\" sizes=\"(max-width: 351px) 100vw, 351px\" \/><\/figure>\n\n\n\n<ul><li>Chlorpromazine, Diphenhydramine, Promethazine<\/li><\/ul>\n\n\n\n<ul><li>In general, short acting \u00e0 sleep onset<\/li><li>However, intermediate and long acting agents \u00e0 residual daytime effects and may produce the somnolence during the day<\/li><li>Data is available for treatment with Z drugs for as long as 6 months without any major adverse effects. Considering the limited availability of trained CBT-I therapist, consensus was reached that in certain circumstances where CBT-I is not possible for any reason, pharmacothepray may be instituted for long term<\/li><li>For short term insomnia, patient should be requested to give <strong>drug holidays intermittently<\/strong> and to restart the treatment when the symptoms appear again. CBT stopped when patient stabilized for atleast 4 weeks<\/li><\/ul>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"357\" height=\"219\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-197.png?w=357\" alt=\"\" class=\"wp-image-609\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-197.png 357w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-197-300x184.png 300w\" sizes=\"(max-width: 357px) 100vw, 357px\" \/><\/figure>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"361\" height=\"255\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-198.png?w=361\" alt=\"\" class=\"wp-image-610\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-198.png 361w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-198-300x212.png 300w\" sizes=\"(max-width: 361px) 100vw, 361px\" \/><\/figure>\n\n\n\n<p><strong>Modafinil <\/strong>\u00e0 block dopamine transporter (DAT)<\/p>\n\n\n\n<ul><li>increase in synaptic dopamine following blockade of DAT leads to increased tonic firing and downstream effects on neurotransmitters including those involved in wakefulness, such as histamine and orexin\/hypocretin.<\/li><\/ul>\n\n\n\n<p><strong>Circadian rhythm sleep-wake disorders (CRSD)<\/strong><\/p>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"345\" height=\"113\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-199.png?w=345\" alt=\"\" class=\"wp-image-611\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-199.png 345w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-199-300x98.png 300w\" sizes=\"(max-width: 345px) 100vw, 345px\" \/><\/figure>\n\n\n\n<ul><li><strong>Melatonin agonist <\/strong><strong>\u00e0 Tasimelteon<\/strong><\/li><\/ul>\n\n\n\n<p><strong>Parasomnias<\/strong><\/p>\n\n\n\n<ul><li>sleep disorders defined as undesirable physical events or experiences that occur during the initiation of sleep, during sleep or during arousal from sleep<\/li><li>REM related parasomnias \u2013 Nightmare disorder, <strong>REM sleep behavior disorder (RBD)<\/strong><\/li><li>NREM related parasomnias \u2013 Sleep walking, sleep terrors, sleep related eating disorder<\/li><li>Other \u00e0 sleep enuresis<\/li><li><strong>The only REM-sleep parasomnia where pharmacotherapy is clearly indicated is RBD<\/strong><\/li><li>Drug of choice for RBD: <strong>Clonazepam and Melatonin<\/strong>; Mechanism of action of melatonin in RBD is not known \u00e0 calmodulin antagonism?<\/li><\/ul>\n\n\n\n<p><strong>Sleep enuresis<\/strong><\/p>\n\n\n\n<ul><li>Bed wetting alarm<\/li><li>Positive reinforcement<\/li><li><strong>Desmopressin<\/strong>: 0.2 mg tablet\/ 20 mcg nasal sprays<\/li><li><strong>Imipramine<\/strong>: 50-75 mg<\/li><\/ul>\n","protected":false},"excerpt":{"rendered":"<p>Pharmacotherapy of Sleep Disorders Sleep is a reversible behavioral state of perceptual&nbsp; disengagement from and unresponsiveness to the environment It constitutes a complex amalgam of physiologic and behavioral processes It is typically accompanied by Postural recumbence Behavioral quiescence Eye closure Problem statement 17 hours of sustained wakefulness &nbsp;blood alcohol level of 0.05% Associated with accidents[&#8230;]\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_seopress_robots_primary_cat":"","_seopress_titles_title":"","_seopress_titles_desc":"","_seopress_robots_index":"","footnotes":""},"categories":[3],"tags":[],"_links":{"self":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts\/602"}],"collection":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/comments?post=602"}],"version-history":[{"count":0,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts\/602\/revisions"}],"wp:attachment":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/media?parent=602"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/categories?post=602"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/tags?post=602"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}