Doxepin in the Treatment of Primary Insomnia: A Placebo-Controlled, Double-Blind, Polysomnographic Study
Abstract
Background Over recent years, the use of antidepressants for the symptomatic treatment of insomnia has grown substantially, but controlled studies are still lacking. Our study is the first investigation to prove objective efficacy and tolerability of low doses of a sedating antidepressant in a randomized, double-blind, and placebo-controlled manner in patients with primary insomnia. Method Forty-seven drug-free patients meeting DSM-IV criteria for primary insomnia (mean +/- SD duration of complaints = 11.2+/-9.7 years) received either 25-50 mg of the tricyclic antidepressant doxepin or placebo for 4 weeks followed by 2 weeks of placebo withdrawal. Sleep was measured by polysomnography at baseline and the first night of application, at 4 weeks of treatment and the first to third night of withdrawal, and after 2 weeks of withdrawal. Results In the doxepin-treated patients who completed the study (N = 20, 47.6+/-11.3), medication significantly increased sleep efficiency after acute (night 1, p Conclusion The results support the effectiveness of low doses of doxepin to improve sleep and working ability in chronic primary insomniacs, although subjective effects were light to moderate, and in some patients, rebound insomnia and specific side effects have to be considered.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Evidence for efficacy of sedating low-dose antidepressants when used alone is relatively weak.
“Evidence for their efficacy when used alone is relatively weak 38-42 and no specific agent within this group is recommended as preferable to the others in this group.”
From Clinical Guideline for the Evaluation and Management of Chronic Insomnia in Adults (2008) · cites this paper as [38]
Cited by
Sorted by citations
Clinical Guideline for the Evaluation and Management of Chronic Insomnia in Adults
Schutte-Rodin, S., Broch, L., Buysse, D., Dorsey, C., & Sateia, M. (2008) · Journal of Clinical Sleep Medicine · doi:10.5664/jcsm.27286 · Cited by 1,943 · see citing works
Sateia, M. J., Buysse, D. J., Krystal, A. D., Neubauer, D. N., & Heald, J. L. (2017) · Journal of Clinical Sleep Medicine · doi:10.5664/jcsm.6470 · Cited by 1,519 · see citing works
Sleep, insomnia, and depression
Riemann, D. W., Krone, L. B., Wulff, K., & Nissen, C. (2019) · Neuropsychopharmacology · doi:10.1038/s41386-019-0411-y · Cited by 863 · see citing works
Self-citationMorin, C. M., Drake, C. L., Harvey, A. G., Krystal, A. D., Manber, R., Riemann, D., & Spiegelhalder, K. (2015) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2015.26 · Cited by 746 · see citing works
Self-citationWilson, S., Nutt, D., Alford, C., Argyropoulos, S., Baldwin, D., Bateson, A., Britton, T., Crowe, C., Dijk, D.-J., Espie, C., et al. (2010) · Journal of Psychopharmacology · doi:10.1177/0269881110379307 · Cited by 634 · see citing works
“Controlled trials have demonstrated an effect of doxepin in insomnia at low dose (25mg) for 4weeks with rebound insomnia (Hajak et al., 2001), and very low ‘microdose’ studies using 1, 2 or 6mg for two nights in adult (Roth et al.”
Self-citationBuscemi, N., Vandermeer, B., Friesen, C., Bialy, L. M., Tubman, M., Ospina, M. B., Klassen, T. P., & Witmans, M. (2005) · PsycEXTRA Dataset · doi:10.1037/e439752005-001 · Cited by 134 · see citing works
Psychiatric Disorders and Sleep
Krystal, A. D. (2012) · Neurologic Clinics · doi:10.1016/j.ncl.2012.08.018 · Cited by 386 · see citing works
A primary care "friendly" cognitive behavioral insomnia therapy.
Edinger, J., & Sampson, W. S. (2003) · Sleep · doi:10.1093/sleep/26.2.177 · Cited by 343 · see citing works
Wilson, S., Anderson, K., Baldwin, D., Dijk, D.-J., Espie, A., Espie, C., Gringras, P., Krystal, A., Nutt, D., Selsick, H., et al. (2019) · Journal of Psychopharmacology · doi:10.1177/0269881119855343 · Cited by 312 · see citing works
“in insomnia at sub-antidepressant dose (25 mg) (Hajak et al., 2001) for four weeks, with rebound insomnia.”
Antidepressants and their effect on sleep
Mayers, A., & Baldwin, D. S. (2005) · Human Psychopharmacology Clinical and Experimental · doi:10.1002/hup.726 · Cited by 313 · see citing works
“Other patient groups Sleep efficiency and sleep quality were significantly improved for insomnia patients taking doxepin (25– 50mg), compared to placebo (Hajak et al., 2001), while doxepin (25mg) was associated with significantly increased total sleep time, and significantly reduced sleep latency and length of nocturn…”
InfluentialSleep Neurobiology from a Clinical Perspective
España, R. A., & Scammell, T. E. (2011) · SLEEP · doi:10.5665/sleep.1112 · Cited by 282 · see citing works
The assessment and management of insomnia: an update
Krystal, A. D., Prather, A. A., & Ashbrook, L. H. (2019) · World Psychiatry · doi:10.1002/wps.20674 · Cited by 256 · see citing works
Wilt, T., MacDonald, R., Brasure, M., Olson, C. M., Carlyle, M., Fuchs, E., Khawaja, I., Diem, S., Koffel, E., Ouellette, J., et al. (2016) · Annals of Internal Medicine · doi:10.7326/m15-1781 · Cited by 229 · see citing works
Voderholzer, U., Al-Shajlawi, A., Weske, G., Feige, B., & Riemann, D. (2003) · Depression and Anxiety · doi:10.1002/da.10101 · Cited by 206 · see citing works
“…from pharmacological studies with antidepressants, which have been proven to be effective in primary insomnia, not only in open trials [Hohagen et al., 1994; Nowell et al., 1999] but also in two randomized, double-blind, and placebo-controlled studies [Hajak et al., 2001; Riemann et al., 2002].”
Self-citationWilson, S. J., & Argyropoulos, S. (2012) · Drugs · doi:10.2165/00003495-200565070-00003 · Cited by 203 · see citing works
Measuring outcomes in randomized clinical trials of insomnia treatments
Morin, C. M. (2003) · Sleep Medicine Reviews · doi:10.1053/smrv.2002.0274 · Cited by 172 · see citing works
Antidepressants for insomnia in adults
Everitt, H., Baldwin, D. S., Stuart, B. L., Lipinska, G., Mayers, A., Malizia, A. L., Manson, C., & Wilson, S. J. (2018) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd010753.pub2 · Cited by 209 · see citing works
Krystal, A., Durrence, H., Scharf, M., Jochelson, P., Rogowski, R., Ludington, E., & Roth, T. (2010) · Sleep · doi:10.1093/sleep/33.11.1553 · Cited by 178 · see citing works
Efficacy and safety of doxepin 1 mg, 3 mg, and 6 mg in adults with primary insomnia.
Roth, T., Rogowski, R., Hull, S. G., Schwartz, H., Koshorek, G., Corser, B., Seiden, D., & Lankford, A. (2007) · Sleep · doi:10.1093/sleep/30.11.1555 · Cited by 172 · see citing works
Effect of sleep apnea on cognition and mood
El-Ad, B., & Lavie, P. (2005) · International Review of Psychiatry · doi:10.1080/09540260500104508 · Cited by 166 · see citing works
Krystal, A. (2009) · Sleep Medicine Reviews · doi:10.1016/j.smrv.2008.08.001 · Cited by 160 · see citing works
Trimipramine in Primary Insomnia: Results of a Polysomnographic Double-Blind Controlled Study
Riemann, D., Voderholzer, U., Cohrs, S., Rodenbeck, A., Hajak, G., Rüther, E., Wiegand, M. H., Laakmann, G., Baghai, T., Fischer, W., et al. (2002) · Pharmacopsychiatry · doi:10.1055/s-2002-34119 · Cited by 145 · see citing works
Self-citationSleep and Antidepressant Treatment
Wichniak, A., Wierzbicka, A., & Jernajczyk, W. (2012) · Current Pharmaceutical Design · doi:10.2174/138161212803523608 · Cited by 142 · see citing works
“Doxepin [172] 47 adults 25-50 4 weeks Placebo PSG Improvement of SE, no change of sleep latency”
BackgroundKrystal, A., Lankford, A., Durrence, H., Ludington, E., Jochelson, P., Rogowski, R., & Roth, T. (2011) · Sleep · doi:10.5665/sleep.1294 · Cited by 139 · see citing works
Doxepin for insomnia: A systematic review of randomized placebo-controlled trials
Yeung, W.-F., Chung, K.-F., Yung, K.-P., & Ng, T. H.-Y. (2015) · Sleep Medicine Reviews · doi:10.1016/j.smrv.2014.06.001 · Cited by 126 · see citing works
Sleep disturbances in depression and the effects of antidepressants
Argyropoulos, S., & Wilson, S. J. (2005) · International Review of Psychiatry · doi:10.1080/09540260500104458 · Cited by 123 · see citing works
“Unfortunately, good quality reports for their subjective effects on sleep exist mainly from primary insomnia rather than depression (Hajak et al., 2001; Riemann et al., 2002).”
Ioachimescu, O., & El-Solh, A. (2008) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656566.2012.683860 · Cited by 122 · see citing works
“Doxepin (in the USA: Adapin , Fisons Pharmaceuticals or Lotus; Prudoxin , Healthpoint; Silenor , Somaxon Pharmaceuticals; Sinequan , Pfizer Roerig; generic doxepin/ doxepin hydrochloride/doxepin HCl [60]) a tricyclic antidepressant that has been available for treating depression for years, has been investigated as a h…”
Clinical practice. Chronic insomnia.
Silber, M. (2005) · New England Journal of Medicine · doi:10.1056/nejmcp043762 · Cited by 122 · see citing works
Sarsour, K., Morin, C. M., Foley, K., Kalsekar, A., & Walsh, J. K. (2010) · Sleep Medicine · doi:10.1016/j.sleep.2009.02.008 · Cited by 121 · see citing works
“[4,5,17,19–21] Nefazodone Serzone <100 mg”
Dombrovski, A. Y., Cyranowski, J. M., Mulsant, B. H., Houck, P. R., Buysse, D. J., Andreescu, C., Thase, M. E., Mallinger, A. G., & Frank, E. (2008) · Depression and Anxiety · doi:10.1002/da.20467 · Cited by 116 · see citing works
“1976), but also sleep quality (Buysse et al. 1996; Feuillade et al. 1992; Hajak et al. 2001; Roth et al. 1982; Shipley et al. 1985) is well established.”
Drug Treatment of Primary Insomnia: A Meta-Analysis of Polysomnographic Randomized Controlled Trials
Winkler, A., Auer, C. J., Doering, B. K., & Rief, W. (2014) · CNS Drugs · doi:10.1007/s40263-014-0198-7 · Cited by 139 · see citing works
Roehrs, T., & Roth, T. (2012) · Neurotherapeutics · doi:10.1007/s13311-012-0148-3 · Cited by 107 · see citing works
Rodenbeck, A., Cohrs, S., Jordan, W., Huether, G., R�ther, E., & Hajak, G. (2003) · Psychopharmacology · doi:10.1007/s00213-003-1565-0 · Cited by 103 · see citing works
“Although in some patients rebound insomnia and specific side effects of doxepin have to be considered (Hajak et al. 2001a), the results give a further rationale for the use of sedating antidepressants in the treatment of sleep complaints.”
InfluentialSelf-citationKrystal, A., Richelson, E., & Roth, T. (2013) · Sleep Medicine Reviews · doi:10.1016/j.smrv.2012.08.001 · Cited by 101 · see citing works
Antidepressants for the Treatment of Insomnia
Wiegand, M. (2012) · Drugs · doi:10.2165/0003495-200868170-00001 · Cited by 101 · see citing works
Anthony, E., Akinmoladun, D., Anochie, D., & Oluyemi, ;. (2001) · doi:10.2307/j.ctt9qgr90.12 · Cited by 95
Lankford, A., Rogowski, R., Essink, B., Ludington, E., Durrence, H., & Roth, T. (2012) · Sleep Medicine · doi:10.1016/j.sleep.2011.09.006 · Cited by 87 · see citing works
“This absence of the typical antihistamine side effects replicates the safety findings from previous clinical trials assessing DXP 66 mg in insomnia patients [14–17]; additionally, these previous sleep laboratory trials did not report evidence of REM suppression [14–17], a finding seen in previous trials assessing dose…”
ResultEffect of Placebo Conditions on Polysomnographic Parameters in Primary Insomnia: A Meta-Analysis
Winkler, A., & Rief, W. (2015) · SLEEP · doi:10.5665/sleep.4742 · Cited by 83 · see citing works
Stahl, S. (2008) · CNS Spectrums · doi:10.1017/s1092852900017089 · Cited by 82 · see citing works
“chronic treatment with these agents at these doses can show loss of hypnotic efficacy and rebound insomnia after sudden discontinuation from chronic treatment (Figure 10).(41) However, selective blockade of Hi receptors at night by very low doses of doxepin is not associated with daytime sedation, either by self repor…”
Pharmacologic treatment of pediatric insomnia.
Owens, J., & Moturi, S. (2009) · Child and Adolescent Psychiatric Clinics of North America · doi:10.1016/j.chc.2009.04.009 · Cited by 81 · see citing works
A meta-analysis of sleep changes associated with placebo in hypnotic clinical trials.
Mccall, W., D'Agostino, R., & Dunn, A. G. (2003) · Sleep Medicine · doi:10.1016/s1389-9457(02)00242-3 · Cited by 73 · see citing works
Histamine-1 receptor antagonism for treatment of insomnia.
Griend, J. V. V., & Anderson, S. L. (2012) · Journal of the American Pharmacists Association · doi:10.1331/japha.2012.12051 · Cited by 70 · see citing works
Sleep Disturbance in Supportive Care of Cancer: A Review
Kvale, E. A., & Shuster, J. L. (2006) · Journal of Palliative Medicine · doi:10.1089/jpm.2006.9.437 · Cited by 73 · see citing works
“Although the data on the utilization of most of these agents for primary insomnia are not compelling, 67–69 there are clinical situations in which their use is appropriate and may spare the use of a separate hypnotic agent.”
Watson, N. F., Benca, R. M., Krystal, A. D., McCall, W. V., & Neubauer, D. N. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12072493 · Cited by 59 · see citing works
“The efficacy and safety of doxepin 25 to 50 mg was compared with placebo in a randomized trial that included a 4-week active treatment period followed by a 2-week single-blind placebo runout [95].”
MethodUpdate on the Safety Considerations in the Management of Insomnia With Hypnotics
Lieberman, J. A. (2007) · The Primary Care Companion to The Journal of Clinical Psychiatry · doi:10.4088/pcc.v09n0105 · Cited by 61 · see citing works
Management of Insomnia in Patients With Chronic Obstructive Pulmonary Disease
George, C., & Bayliff, C. (2012) · Drugs · doi:10.2165/00003495-200363040-00004 · Cited by 56 · see citing works
“minimal risk of rebound insomnia in patients with insomnia.[55] Unfortunately, the drug has not been studied in patients with COPD but, given the suggestion that antidepressant medications may be useful in managing dyspnea in patients with COPD, future trials are warranted.”
Enhanced analgesic activity by cyclodextrins – a systematic review and meta-analysis
Brito, R., Araújo, A., Quintans, J., Sluka, K., & Quintans-Júnior, L. (2015) · Expert Opinion on Drug Delivery · doi:10.1517/17425247.2015.1046835 · Cited by 55 · see citing works
“DOX, a member of tricyclic antidepressant family, is used as analgesic in addition to depression and anxiety disorders [81-83].”
Tal, J. Z., Suh, S. A., Dowdle, C. L., & Nowakowski, S. (2014) · Current Psychiatry Reviews · doi:10.2174/1573400510666140929194848 · Cited by 53 · see citing works
“Doxepin has been shown to have both sleep initiation and maintenance improvements in the nights following use in several randomized control trials in both middle and older aged adults, as assessed by PSG [111-115].”
Sleep-Related Disorders in Neurology and Psychiatry
Rémi, J., Pollmächer, T., Spiegelhalder, K., Trenkwalder, C., & Young, P. (2019) · Deutsches Ärzteblatt international · doi:10.3238/arztebl.2019.0681 · Cited by 59 · see citing works
Optimizing the Pharmacologic Treatment of Insomnia: Current Status and Future Horizons
Minkel, J., & Krystal, A. (2013) · Sleep Medicine Clinics · doi:10.1016/j.jsmc.2013.06.002 · Cited by 52 · see citing works
Meta‐analysis of sleep changes in control groups of insomnia treatment trials
Bélanger, L., Vallières, A., Ivers, H., Moreau, V., Lavigne, G., & Morin, C. (2007) · Journal of Sleep Research · doi:10.1111/j.1365-2869.2007.00566.x · Cited by 52 · see citing works
“trials and conclusions as to whether insomnia is reactive to placebo interventions remain mitigated (Bixler et al., 1995; Hajak et al., 2001; McCall et al., 2003; McCall et al., 2005; Roehrs et al., 1985; Roehrs et al., 1990; Walsh et al., 2000).”
Antidepressant use in psychiatry and medicine: importance for dental practice.
Keene, J., Galasko, G., & Land, M. F. (2003) · The Journal of the American Dental Association (1939) · doi:10.14219/jada.archive.2003.0019 · Cited by 49 · see citing works
Prevalence and factors associated with off-label antidepressant prescriptions for insomnia
Lai, L., Tan, M. H., & Lai, Y.-C. (2011) · Drug, Healthcare and Patient Safety · doi:10.2147/dhps.s21079 · Cited by 46 · see citing works
New guidelines for diagnosis and treatment of insomnia
Pinto, L. R., Alves, R. C., Caixeta, E. C., Fontenelle, J. A., Bacellar, A., Poyares, D. R., Alóe, F., Rizzo, G. N. V., Minhoto, G. R., Bittencourt, L., et al. (2010) · Arquivos de Neuro-Psiquiatria · doi:10.1590/s0004-282x2010000400038 · Cited by 51 · see citing works
Pan, B., Ge, L., Lai, H., Hou, L., Tian, C., Wang, Q., Yang, K., Lü, Y., Zhu, H., Li, M., et al. (2023) · Drugs · doi:10.1007/s40265-023-01859-8 · Cited by 44 · see citing works
Liu, Y., Xu, X.-M., Dong, M.-X., Jia, S., & Wei, Y.-D. (2017) · Sleep Medicine · doi:10.1016/j.sleep.2017.03.007 · Cited by 39 · see citing works
“Nine trials [23-31] w e r e found to m eet the inclusion criteria a n d were included in the meta-analysis (Figure 1).”
Pharmacologic management of insomnia: past, present, and future.
Curry, D. T., Eisenstein, R. D., & Walsh, J. (2006) · Psychiatric Clinics of North America · doi:10.1016/j.psc.2006.09.006 · Cited by 38 · see citing works
Antidepressant and Antipsychotic Drugs
Krystal, A. D. (2010) · Sleep Medicine Clinics · doi:10.1016/j.jsmc.2010.08.010 · Cited by 47 · see citing works
Management of insomnia: update and new approaches
Riemann, D. W. (2010) · Nature and Science of Sleep · doi:10.2147/nss.s6642 · Cited by 23 · see citing works
Self-citationDSC kinetic study of the incompatibility of doxepin with dextrose
Ghaderi, F., Nemati, M., Siahi-Shadbad, M., Valizadeh, H., & Monajjemzadeh, F. (2016) · Journal of Thermal Analysis and Calorimetry · doi:10.1007/s10973-015-4995-0 · Cited by 31
Insomnia, hypnotic use, and health-related quality of life in a nationally representative sample
Scalo, J., Desai, P., & Rascati, K. L. (2014) · Quality of Life Research · doi:10.1007/s11136-014-0842-1 · Cited by 33 · see citing works
“For example, a 4-week trial of doxepin (n = 20) versus placebo (n = 20) found improved visual analog scale ratings for ‘working ability,’ but no difference in ‘energy’ ratings [17].”
Wang, Y.-Q., Takata, Y., Li, R.-X., Zhang, Z., Zhang, M.-Q., Urade, Y., Qu, W.-M., & Huang, Z.-L. (2015) · Pharmacology, Biochemistry and Behavior · doi:10.1016/j.pbb.2014.12.002 · Cited by 31 · see citing works
“It has significant anti-histaminergic activity and is sometimes used to treat insomnia (Hajak et al., 2001; Weber et al., 2010).”
Selecting a pharmacotherapy regimen for patients with chronic insomnia
Hassinger, A. B., Bletnisky, N., Dudekula, R., & El-Solh, A. (2020) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2020.1743265 · Cited by 32 · see citing works
“minimal associated next-day residual effects [40].”
The Molecular Basis of Insomnia: Implication for Therapeutic Approaches
Wang, Z., & Liu, J. (2016) · Drug Development Research · doi:10.1002/ddr.21338 · Cited by 29 · see citing works
“Low dose doxepin shortened sleep latency, increased total sleep time and increased sleep quality in insomniacs [Hajak et al., 2001; Krystal et al., 2010] and has been approved for the treatment of primary insomnia.”
Healthcare use in adults with insomnia: a longitudinal study.
Hayward, R., Jordan, K., & Croft, P. (2010) · The British journal of general practice : the journal of the Royal College of General Practitioners · doi:10.3399/bjgp10x501822 · Cited by 30 · see citing works
“Wake up several times a night 561 (26) 383 (43) 158 (14)”
Wolff, J., Reißner, P., Hefner, G., Normann, C., Kaier, K., Binder, H., Hiemke, C., Toto, S., Domschke, K., Marschollek, M., et al. (2021) · PLoS ONE · doi:10.1371/journal.pone.0255192 · Cited by 34 · see citing works
“Instead, they might have been used to address insomnia [62,63], control agitation and aggressive behaviour [64] or to treat comorbid psychotic symptoms.”
BackgroundTolerability of Hypnosedatives in Older Patients
Wortelboer, U., Cohrs, S., Rodenbeck, A., & Rüther, E. (2002) · Drugs & Aging · doi:10.2165/00002512-200219070-00006 · Cited by 29 · see citing works
Self-citationLow-dose doxepin for the treatment of insomnia: emerging data
Goforth, H. (2009) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656560903005587 · Cited by 27 · see citing works
“The impact of doxepin upon subjective outcome measures seemed more mixed, and subjective WASO (sWASO) was not significantly different at any dose.”
InfluentialNovel therapeutic usage of low-dose doxepin hydrochloride
Singh, H., & Becker, P. (2007) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.16.8.1295 · Cited by 27 · see citing works
Hypnotika – Stand der Forschung
Nissen, C., Frase, L., Hajak, G., & Wetter, T. (2013) · Der Nervenarzt · doi:10.1007/s00115-013-3893-6 · Cited by 26 · see citing works
Self-citation2023 Guidelines on the Diagnosis and Treatment of Insomnia in Adults - Brazilian Sleep Association
Drager, L. F., Assis, M., Bacelar, A. F. R., Poyares, D. L. R., Conway, S. G., Pires, G. N., de Azevedo, A. P., Carissimi, A., Eckeli, A. L., Pentagna, Á., et al. (2023) · Sleep Science · doi:10.1055/s-0043-1776281 · Cited by 25 · see citing works
“224 – 228 The systematic review published in 2015 with RCTs comparing doxepin with placebo 229 concluded that doxepin had a mean effect size compared with placebo for sleep maintenance and sleep duration, without signi fi cant residue the next day, being considered safe and effective, particularly…”
BackgroundDissection of the Factors Driving the Placebo Effect in Hypnotic Treatment of Depressed Insomniacs
Mccall, W., D'Agostino, R., Rosenquist, P., Kimball, J., Boggs, N., Lasater, B., & Blocker, J. N. (2011) · Sleep Medicine · doi:10.1016/j.sleep.2011.03.008 · Cited by 25 · see citing works
“Indeed, as recently as a decade ago, some investigators argued that there was no placebo effect in insomnia clinical trials [6–9].”
Pharmacologic Treatment of Primary Insomnia
Hall-Porter, J. M., Curry, D. T., & Walsh, J. K. (2010) · Sleep Medicine Clinics · doi:10.1016/j.jsmc.2010.08.006 · Cited by 31 · see citing works
Chronic tinnitus and associated sleep disturbances
Burgos, I., Feige, B., Hornyak, M., Härter, M., Weske-Heck, G., Voderholzer, U., & Riemann, D. (2005) · Somnologie - Schlafforschung und Schlafmedizin · doi:10.1111/j.1439-054x.2005.00056.x · Cited by 23 · see citing works
Self-citationNew approaches for the treatment of sleep disorders.
DeMartinis, N., Kamath, J., & Winokur, A. (2009) · Advances in Pharmacology · doi:10.1016/s1054-3589(08)57005-0 · Cited by 23 · see citing works
Chapter 37 – Clinical Pharmacology of Other Drugs Used as Hypnotics
Buysse, D. J., Schweitzer, P., & Moul, D. (2005) · Elsevier eBooks · doi:10.1016/b0-72-160797-7/50044-6 · Cited by 23 · see citing works
Paulzen, M., Haen, E., Hiemke, C., Fay, B., Unholzer, S., Gründer, G., & Schoretsanitis, G. (2018) · Journal of Affective Disorders · doi:10.1016/j.jad.2017.11.046 · Cited by 21 · see citing works
Ghaderi, F., Nemati, M., Siahi-Shadbad, M., Valizadeh, H., & Monajjemzadeh, F. (2015) · doi:10.1016/j.powtec.2015.09.007 · Cited by 21
Longitudinal Follow up of Primary Insomnia Patients in a Psychiatric Clinic
Fong, S., & Wing, Y. K. (2007) · Australian and New Zealand journal of psychiatry (Print) · doi:10.1080/00048670701400016 · Cited by 21 · see citing works
Paroxetine treatment of primary insomnia in older adults.
Reynolds, C., Buysse, D. J., Miller, M. D., Pollock, B., Hall, M., & Mazumdar, S. (2006) · The American journal of geriatric psychiatry · doi:10.1097/01.jgp.0000218327.21111.de · Cited by 19 · see citing works
What is “evidence” in psychotherapies?
Lilienfeld, S. (2019) · World Psychiatry · doi:10.1002/wps.20654 · Cited by 18 · see citing works
Nichterholsamer Schlaf und Insomnie
Riemann, D., Voderholzer, U., & Berger, M. (2003) · Der Nervenarzt · doi:10.1007/s00115-003-1524-3 · Cited by 18 · see citing works
Self-citationThe guidelines for ‘non-restorative sleep’: Relevance for the diagnosis and therapy of insomnia
Riemann, D., Fischer, J., Mayer, G., & Peter, H. J. (2003) · Somnologie - Schlafforschung und Schlafmedizin · doi:10.1046/j.1439-054x.2003.03201.x · Cited by 17 · see citing works
Self-citationClinical Sleep–Wake Disorders II: Focus on Insomnia and Circadian Rhythm Sleep Disorders
Spiegelhalder, K., Nissen, C., & Riemann, D. W. (2017) · Handbook of experimental pharmacology · doi:10.1007/164_2017_40 · Cited by 20 · see citing works
Self-citationDoxepin in children and adolescents with symptoms of insomnia: A single-center experience
Shah, Y., Stringel, V., Pavkovic, I., & Kothare, S. (2020) · Journal of Clinical Sleep Medicine (JCSM) · doi:10.5664/jcsm.8338 · Cited by 16 · see citing works
“In another randomized controlled trial, a single dose of doxepin 25 or 50mg did improve associated sleep difficulties in patients with chronic primary insomnia.(28) In our study, we observed that there was improvement in terms of both sleep initiation and maintenance.”
Die Bedeutung des Schlafs für gesunde Alkoholkonsumenten und alkoholabhängige Patienten
Gann, P. H., van Calker, D., Feige, B., & Riemann, D. (2004) · Der Nervenarzt · doi:10.1007/s00115-003-1637-8 · Cited by 16 · see citing works
Self-citationThe condition of insomnia: Etiopathogenetic considerations and their impact on treatment practices
Dikeos, D., & Soldatos, C. (2005) · International Review of Psychiatry · doi:10.1080/09540260500104466 · Cited by 13 · see citing works
“This is particularly the case for trazodone (Mendelson et al., 2004), doxepin (Hajak et al., 2001; Rodenbeck et al., 2003) and mirtazapine (Barkin, Chor, Braun & Schwer, 1999), although their efficacy, dose-response, tolerance, and benefit/ harm ratio have not been established in insomniacs…”
Nefazodone in primary insomnia: an open pilot study.
Wiegand, M., Galanakis, P., & Schreiner, R. (2004) · Progress in Neuro-psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2004.05.042 · Cited by 13 · see citing works
“For two compounds only, there is evidence from randomized, placebo-controlled trials proving their efficacy in primary insomnia: doxepin (Hajak et al., 2001) confirming data from a preceding open study (Hajak et al., 1996), and trimipramine (Riemann et al., 2002) confirming preceding single-blind…”
ResultPharmacologic Treatment of Primary Insomnia
Walsh, J. K., Roehrs, T., & Roth, T. G. (2005) · Elsevier eBooks · doi:10.1016/b0-72-160797-7/50070-7 · Cited by 52 · see citing works
Chapter 42 – Clinical Pharmacology of Other Drugs Used as Hypnotics
Buysse, D. J., & Tyagi, S. (2017) · Elsevier eBooks · doi:10.1016/b978-0-323-24288-2.00042-8 · Cited by 12 · see citing works
Alcohol, toxins, and medications as a cause of sleep dysfunction
Conroy, D. A., & Brower, K. J. (2010) · Handbook of clinical neurology · doi:10.1016/b978-0-444-52006-7.00038-1 · Cited by 14 · see citing works
Woo, J., Ha, T.-W., Kang, J., Hong, J., & Oh, K. (2016) · Korean Journal of Physiology and Pharmacology · doi:10.4196/kjpp.2017.21.1.27 · Cited by 11
“We considered that DCA would be inhibitory in the CNS. DCA also prolonged sleeping time, and decreased the sleep latency by pentobarbital (42 mg/kg), in a dose- Fig.”
InfluentialCrescenzo, F. D., Foti, F., Ciabattini, M., Giovane, C. D., Watanabe, N., Schepisi, M. S., Quested, D. J., Cipriani, A., Barbui, C., & Amato, L. (2016) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd012364 · Cited by 13 · see citing works
Wu, J.-F., Chang, F., & Zu, H.-B. (2015) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2015.2686 · Cited by 11 · see citing works
“Doxepin has marked inhibitory effects on neurotransmitter receptors, including the histamine, serotonin, α 1 adrenergic and muscarinic acetylcholine receptors (12), and has been shown to strongly promote the initiation and maintenance of sleep and to improve sleep quality (11,12).”
Subjektive Parameter des Schlafs bei Patienten mit primärer Alkoholabhängigkeit
Gann, H., Landbrecht, M., Feige, B., Hohagen, F., & Riemann, D. (2001) · doi:10.1046/j.1439-054x.2001.01151.x · Cited by 10
Self-citationWang, F., He, J.-J., Zhou, Y.-L., Ye, L., Li, B., Ma, Z., Chen, C., Zhang, R.-X., Lin, Z., Tang, J.-S., et al. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1226014 · Cited by 9 · see citing works
Owen, N. E., Barker, R. A., & Voysey, Z. J. (2023) · Journal of Huntington s Disease · doi:10.3233/jhd-230567 · Cited by 13 · see citing works
“Doxepin has also been shown to increase total sleep time and overall sleep efficiency in young, middle-aged, and elderly primary insomnia patients [76-78].”
BackgroundLing, S., & Swaab, D. (2021) · Current Neuropharmacology · doi:10.2174/1570159x19666210909144930 · Cited by 9 · see citing works
“Several other studies showed similar improvement in sleep maintenance and sleep duration with doxepin compared to placebo [61-65].”
Diagnosis and treatment of chronic insomnia
Saddichha, S. (2010) · Annals of Indian Academy of Neurology · doi:10.4103/0972-2327.64628 · Cited by 9 · see citing works
“Evidence for their effi cacy when used alone is relatively weak and hence no specifi c agent within this group is recommended as preferable to the others in this group.[58-61]”
Efficacy and Safety of Sleep-Promoting Agents
Roth, T., & Roehrs, T. (2008) · Sleep Medicine Clinics · doi:10.1016/j.jsmc.2008.03.001 · Cited by 9 · see citing works
- Authors
- Hajak, G., Rodenbeck, A., Voderholzer, U., Riemann, D., Cohrs, S., Hohagen, F., Berger, M., & Ruther, E.
- Venue
- The Journal of Clinical Psychiatry
- Publisher
- Physicians Postgraduate Press, Inc
- Published
- 2001-06-15
- Volume
- 62
- Issue
- 6
- Pages
- 453-463
- ISSN
- 0160-6689 (ISSN-L)
- OpenAlex
- W2060370838
- Cited by
- 199
- References
- 0
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 2 · 2023: 6 · 2022: 6 · 2021: 5 · 2020: 4 · 2019: 9 · 2018: 3 · 2017: 9 · 2016: 8 · 2015: 13 · 2014: 11 · 2013: 11 · 2012: 8
- FWCI
- 9.46
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- University of Regensburg Publication Server (University of Regensburg) (acceptedVersion)
- FreiDok plus (Universitätsbibliothek Freiburg) (submittedVersion)
- Topics
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Physiology › Obstructive Sleep Apnea Research
- Keywords
- doxepin, primary insomnia, tricyclic antidepressants, sedating antidepressants, sleep efficiency, rebound insomnia, sleep quality, work ability, drug tolerability, chronic insomnia
- MeSH terms
- Antidepressive Agents, Tricyclic, Chronic Disease, Dose-Response Relationship, Drug, Double-Blind Method, Doxepin, Drug Administration Schedule, Female, Health Status, Humans, Sleep Initiation and Maintenance Disorders, Male, Middle Aged, Patient Dropouts, Placebos, Psychiatric Status Rating Scales, Severity of Illness Index, Sleep, Treatment Outcome, Polysomnography
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
