The DOI matches its Crossref record.
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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
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?
In the citing paper
“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]
In the citing paper
“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 nocturnal awakenings, compared to placebo with insomnia patients and healthy volunteers (Hajak et al., 1996).”
From Antidepressants and their effect on sleep (2005) · cites this paper as Hajak et al., 2001
Citations
Cited by
Sorted by citations
Items 101–174 of 174
Influence of low-dose doxepin on periodic leg movements in sleep in primary insomnia patients
Hornyak, M., Kopasz, M., Rodenbeck, A., Hajak, G., Riemann, D., & Voderholzer, U. (2005) · Somnologie - Schlafforschung und Schlafmedizin · doi:10.1111/j.1439-054x.2005.00050.x · Cited by 9
Self-citationSchlaf und Schlafstörungen beim alten Menschen
Schlitzer, J., Heubaum, S., & Frohnhofen, H. (2014) · Zeitschrift für Gerontologie und Geriatrie (Print) · doi:10.1007/s00391-014-0810-y · Cited by 8
Farjami, F., Fasihi, F., Alimohammadi, F., & Moradi, S. E. (2019) · Iranian journal of pharmaceutical research · doi:10.22037/ijpr.2019.2342 · Cited by 8
Hypnosedatives and anxiolytics
Curran, S., & Musa, S. (2001) · doi:10.1016/s0378-6080(01)80010-6 · Cited by 8
Mehra, A., Khanna, J., Singh, G., Sachdeva, V., & Bedi, N. (2025) · Current Behavioral Neuroscience Reports · doi:10.1007/s40473-025-00308-y · Cited by 8
Efficacy of Hypnotic Medications and Other Medications Used for Insomnia
Feren, S. D., Katyal, A., & Walsh, J. (2006) · Sleep Medicine Clinics · doi:10.1016/j.jsmc.2006.06.011 · Cited by 7
Treatment of insomnia in elderly patients
Kneginja, R., Kellner, S., Lenche, M., & Helmut, F. (2020) · Journal for ReAttach Therapy and Developmental Diversities · doi:10.26407/2019jrtdd.1.25 · Cited by 6
Sleep Pharmacogenetics: The Promise of Precision Medicine.
Krystal, A., & Prather, A. (2019) · Sleep Medicine Clinics · doi:10.1016/j.jsmc.2019.05.003 · Cited by 6
Mechanism underlying the effects of doxepin on β-amyloid -induced memory impairment in rats.
Bu, J., & Zu, H. (2017) · PubMed Central · doi:10.22038/ijbms.2017.9274 · Cited by 5
“Local application of doxepin has therapeutic effects in atopic dermatitis (8) and it is used as second-line therapy for chronic urticarial (9).”
Reisi, P., Eidelkhani, N., Radahmadi, M., Kazemi, M., Rafiee, L., & Alaei, H. (2015) · Advanced Biomedical Research · doi:10.4103/2277-9175.166139 · Cited by 5
“It is used to treat depression and anxiety disorders.[15] Up to now various properties of doxepin have been reported, such as anti‐inflammatory[16] and anticonvulsant effects.”
Effects of different doses of doxepin on passive avoidance learning in rats
Reisi, P., Gharzi, M., Dolatabadi, H. R. D., & Javanmard, S. (2013) · Advanced Biomedical Research · doi:10.4103/2277-9175.115823 · Cited by 7
“Doxepin also has been known as second‐line therapy for chronic urticaria.[20] Various properties of doxepin have been reported; among them we can mention the anticonvulsant effects.”
Emerging pharmacotherapeutic agents for insomnia: a hypnotic panacea?
Navab, P., & Guilleminault, C. (2006) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656566.7.13.1731 · Cited by 6
“[18] conducted a 4-week, double-blind, placebo-controlled trial specifically on doxepin 25 and 50 mg, utilising both polysomnography and subjective data.”
Clinical Pharmacology of Other Drugs Used as Hypnotics
Buysse, D. J. (2011) · Elsevier eBooks · doi:10.1016/b978-1-4160-6645-3.00043-8 · Cited by 8
Therapie der Insomnie im höheren Lebensalter
Richter, K., Kellner, S., Miloseva, L., & Frohnhofen, H. (2020) · Zeitschrift für Gerontologie und Geriatrie (Print) · doi:10.1007/s00391-019-01684-3 · Cited by 5
Pharmacological Treatment of Nocturnal Sleep Disturbances
Wilson, S. J., & Nutt, D. (2010) · doi:10.1002/9781444315158.ch5 · Cited by 5
Chapter 88 – Pharmacologic Treatment of Insomnia: Other Medications
Krystal, A. (2017) · Elsevier eBooks · doi:10.1016/b978-0-323-24288-2.00088-x · Cited by 5
Conrad, M., Söldner, C. A., & Sticht, H. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23031420 · Cited by 4
Schlaf und Schlafstörungen beim alten Menschen
Frohnhofen, H., Schlitzer, J., & Netzer, N. C. (2017) · Somnologie - Schlafforschung und Schlafmedizin · doi:10.1007/s11818-017-0102-z · Cited by 4
“Ältere Menschen mit Insomnie stürzen häufiger, zeigen häufiger kognitive Probleme, sind in ihrer Leistungsfähigkeit und Selbstversorgungsfähigkeit deutlicher beeinträchtigt und haben eine höhere Mortalität als ältere Menschen ohne Insomnie [7, 13, 20, 23, 24, 25].”
Antidepressant management of insomnia disorder in the absence of a mood disorder
Nazarian, P. K., & Park, S. H. (2014) · Mental Health Clinician · doi:10.9740/mhc.n188364 · Cited by 5
“One of the earlier doxepin studies for primary insomnia in adults utilized 25-50mg for 4 weeks, improving TST in 20 adults.(39) Subsequent controlled studies systematically assessed significantly lower doses of doxepin for its effects on sleep.”
Häufige schlafmedizinische Erkrankungen
Mayer, G. (2011) · Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz · doi:10.1007/s00103-011-1376-0 · Cited by 4
Evaluation and Management of Insomnia in the Psychiatric Setting
Doghramji, K., Grewal, R. G., & Markov, D. (2009) · FOCUS The Journal of Lifelong Learning in Psychiatry · doi:10.1176/foc.7.4.foc441 · Cited by 5
The Neuropharmacology of Sleep Disorders: Better Sleeping Through Chemistry?
Suhl, J. (2007) · Journal of Pharmacy Practice · doi:10.1177/0897190007305149 · Cited by 4
“Doxepin has been shown to improve sleep parameters and subjective sleep quality of chronic insomniacs in a placebo-controlled, 4-week trial.(31) In addition, doxepin was more effective than placebo at normalizing the elevated cortisol levels commonly seen in chronic insomnia.”
Ancoli-Israel, S., Folks, D., Krystal, A., & Mccall, W. (2006) · doi:10.1111/j.1532-5415.2005.00575_2.x · Cited by 4
“The Editors note that the Food and Drug Administration has now approved eszopiclone.(6) The conclusion notes that ‘‘popular hypnotics’’ have several drawbacks then notes that ‘‘emerging’’ hypnotics ‘‘may offer unique advantages.”
Clinical Psychopharmacology for Neurologists
Grossberg, G., & Kinsella, L. (2018) · Cambridge International Law Journal · doi:10.1007/978-3-319-74604-3 · Cited by 4
“Psychotherapy also effectively prevents relapse when continued after acute phase treatment with pharmacotherapy [61].”
Therapeutic efficacy of zolpidem combined with cognitive-behavioral therapy on primary insomnia
Song, Y., & Liang, B. (2019) · Medicine · doi:10.1097/md.0000000000017122 · Cited by 3
Low-dose doxepin (3 and 6 mg) for the treatment of insomnia
Lankford, A. (2011) · Future Neurology · doi:10.2217/fnl.10.83 · Cited by 3
“conducted the first randomized, double-blind, placebo-controlled investigation to measure objective efficacy and tolerability in treating primary insomnia with a low-dose sedating antidepressant [38].”
BackgroundMEGESTROL ACETATE FOR GERIATRIC ANOREXIA/CACHEXIA
Haren, M. T., Kim, M., & Kevorkian, R. (2006) · Journal of The American Geriatrics Society · doi:10.1111/j.1532-5415.2005.00575_3.x · Cited by 3
Alonso, I., & España, R. A. (2021) · Reference Module in Neuroscience and Biobehavioral Psychology · doi:10.1016/b978-0-12-378610-4.00102-9 · Cited by 3
Phillips, K., & Gunther, M. (2015) · Springer eBooks · doi:10.1007/978-1-4939-2089-1_22 · Cited by 3
Feren, S. D., Schweitzer, P., & Walsh, J. (2011) · Handbook of Clinical Neurology · doi:10.1016/b978-0-444-52007-4.00005-9 · Cited by 3
Pharmacological Treatment of Insomnia
Schweitzer, P. K., Curry, D. T., Eisenstein, R. D., & Walsh, J. K. (2010) · Humana Press eBooks · doi:10.1007/978-1-60327-042-7_23 · Cited by 9
Sangal, R. (2018) · Clinical EEG and Neuroscience · doi:10.1177/1550059417709882 · Cited by 2
Pharmacological Treatment of Insomnia and Parasomnias
Reading, P., & Wilson, S. J. (2018) · Sleep Disorders in Neurology · doi:10.1002/9781118777251.ch5 · Cited by 2
Diagnostik und Therapie von Schlafstörungen
Spiegelhalder, K., & Riemann, D. (2009) · Fortschritte der Neurologie Psychiatrie · doi:10.1055/s-0028-1109130 · Cited by 2
Self-citationNeuroleptika und Antidepressiva als Hypnotika. Wenn Nebenwirkungen zur Hauptwirkung werden
Enzensperger, C., & Lehmann, J. (2007) · Pharmazie in unserer Zeit · doi:10.1002/pauz.200600217 · Cited by 4
Pharmakotherapie der Insomnien: State of the Art
Perlis, M. L., Spiegelhalder, K., Voderholzer, U., Hornyak, M., Klöpfer, C., Berger, M., Hajak, G., & Riemann, D. (2007) · Somnologie - Schlafforschung und Schlafmedizin · doi:10.1007/s11818-007-0300-1 · Cited by 2
Self-citationSedierende Antidepressiva in der Behandlung von Patienten mit primärer Insomnie
Lange, K., Geisler, P., Klein, H., & Hajak, G. (2007) · Psychiatrische Praxis · doi:10.1055/s-2006-940217 · Cited by 2
Self-citationPsychoneuroendokrine Pathomechanismen der psychophysiologischen Insomnie
Rodenbeck, A., Hajak, G., Meier, A., Cohrs, S., & Jordan, W. (2005) · Somnologie - Schlafforschung und Schlafmedizin · doi:10.1111/j.1439-054x.2004.00041.x · Cited by 2
Self-citationSleep Disorder Prediction using Advanced Machine Learning Techniques
Sarala, P., Charitha, C., Kala, C. K., Yaswanthi, A., & Haq, A. (2025) · International Journal for Sciences and Technology · doi:10.71097/ijsat.v16.i1.2182 · Cited by 1
Zhang, M., Huang, F., Jiang, F.-Y., Mai, M., Guo, X., Zhang, Y., Xu, Y., & Zu, H.-B. (2022) · Medicine · doi:10.1097/md.0000000000031201 · Cited by 1
“[15] Anecdotal reports have shown that patients taking higher doses of doxepin are more likely to have anticholinergic effects, increased appetite, and weight.[16] On the contrary, low-dose doxepin does not show significant anticholinergic effects or results in severe adverse reactions.”
BackgroundRibeill, Y. (2013) · Wiley eBooks · doi:10.1002/9781118532331.ch1 · Cited by 2
Insomnia: assessment and treatment review
Qazi, F. M., & Schluederberg, E. A. (2012) · Osteopathic Family Physician · doi:10.1016/j.osfp.2012.03.002 · Cited by 1
Thum, A., Hemmeter-Spernal, J., & Hemmeter, M. (2011) · Schweizer Archiv für Neurologie und Psychiatrie · doi:10.4414/sanp.2011.02254 · Cited by 1
Ein neues standardisiertes Kurzzeitprogramm zur Behandlung von Schlafstörungen bei Tinnituspatienten
Crönlein, T., Langguth, B., Täuber, S., Kurzbuch, K., Kleinjung, T., Geisler, P., Klein, H. E., & Hajak, G. (2010) · University of Regensburg Publication Server (University of Regensburg) · doi:10.5283/pf.42 · Cited by 1
“Auch wenn Antidepressiva bei Insomnien helfen können [20, 25], gibt es Patienten, welche therapieresistent sind oder diese wegen Unverträglichkeit ablehnen.”
Self-citationEvidenzbasierte Medizin und die Cochrane Collaboration— Bedeutung für die Schlafmedizin
Berner, M., Berger, M., & Riemann, D. (2001) · Somnologie - Schlafforschung und Schlafmedizin · doi:10.1046/j.1439-054x.2001.01143.x · Cited by 1
Self-citationHypnotics: Definition, Classifications, Indications, and Differential Indications
Dietmaier, O. (2021) · NeuroPsychopharmacotherapy · doi:10.1007/978-3-319-56015-1_432-1 · Cited by 1
Krystal, A. D. (2011) · Elsevier eBooks · doi:10.1016/b978-1-4377-1703-7.10054-4 · Cited by 2
[Recent and potential drugs for treatment of insomnia].
Terao, A., & Miyamoto, M. (2007) · Nihon yakurigaku zasshi. Folia pharmacologica Japonica · doi:10.1254/fpj.129.35 · Cited by 1
Chen, K., & Maroney, M. E. (2025) · Mental Health Clinician · doi:10.9740/mhc.2025.04.051
An Experimental Test of Viewing the Past Based on Cosmic Memory
A’assam, A. A., & Jawad, L. M. (2024) · International Journal For Multidisciplinary Research · doi:10.36948/ijfmr.2024.v06i02.17961
Krystal, A. D., & Prather, A. (2020) · Clinics Collections · doi:10.1016/j.ccol.2020.07.019
Rastogi, P., & Rastogi, D. (2015) · Journal of Evolution of Medical and Dental Sciences · doi:10.14260/jemds/2015/2241
Pharmacologic Treatment of Insomnia
Neubauer, D. N. (2008) · Wiley eBooks · doi:10.1002/9780470515167.ch105 · Cited by 1
Pharmacologic Treatment of Insomnia
Neubauer, D. N., Minkel, J. D., & Krystal, A. D. (2015) · Wiley eBooks · doi:10.1002/9781118753378.ch107
Wann sind medikamentöse Therapien indiziert?
Frase, L., & Nissen, C. (2013) · DNP - Der Neurologe und Psychiater · doi:10.1007/s15202-013-0251-2
“Hajak G, Rodenbeck A, Voderholzer U, Rie mann D, Cohrs S, Hohagen F et al. Doxepin in the treatment of primary insomnia: a pla cebocontrolled, doubleblind, polysomno graphic study.”
Roth, T., & Roehrs, T. (2010) · Sleep Medicine Clinics · doi:10.1016/j.jsmc.2010.09.002
Current Advances in the Pharmacotherapy of Insomnia: Pipeline Agents
Sateia, M. (2010) · Medical psychiatry · doi:10.3109/9781420080803.037
Serotonergic drugs as sleep medications
Serretti, A., & Drago, A. (2008) · doi:10.3109/9780203091715-27
Trizyklische Antidepressiva als Schlafmittel. Medikamentöse Behandlungsoptionen bei Insomnie
Doerr, J., & Riemann, D. (2008) · Pharmazie in unserer Zeit · doi:10.1002/pauz.200800266
Self-citationDoerr, J., Hajak, G., & Riemann, D. (2008) · psychoneuro · doi:10.1055/s-2008-1066870
Self-citationDoerr, J., Spiegelhalder, K., & Riemann, D. (2007) · Psychiatrie und Psychotherapie up2date · doi:10.1055/s-2007-986230
Self-citationJohnson, K., Mansukhani, M. P., & Kolla, B. P. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-820472-6.00181-x
Pharmacologic treatment of insomnia
Harris, S., Thorpy, M., & Monderer, R. (2021) · Reference Module in Neuroscience and Biobehavioral Psychology · doi:10.1016/b978-0-12-822963-7.00101-8
Redden, W. M. (2018) · Springer eBooks · doi:10.1007/978-3-319-74604-3_6
Markov, D., & Doghramji, K. (2015) · Milestones in drug therapy · doi:10.1007/978-3-319-11514-6_5
Pharmakotherapie der Insomnie im höheren Lebensalter
Schlitzer, J., Heubaum, S., & Frohnhofen, H. (2014) · Schlaf · doi:10.1055/s-0038-1626102
“Hajak G, et al. Doxepin in the treatment of primary insomnia: a placebo-controlled, double-blind, polysomnographic study.”
InfluentialPharmacologic Treatment of Insomnia
Monderer, R., Harris, S., & Thorpy, M. (2013) · Elsevier eBooks · doi:10.1016/b978-0-12-378610-4.00200-x
Chowdhuri, S. (2011) · Humana Press eBooks · doi:10.1007/978-1-60761-735-8_2
Spiegelhalder, K., Hirscher, V., Unbehaun, T., Hajak, G., & Riemann, D. W. (2012) · Elsevier eBooks · doi:10.1016/b978-3-437-24903-7.10018-6
Self-citationChapter 82 – Pharmacologic Treatment: Other Medications
Krystal, A. (2011) · Elsevier eBooks · doi:10.1016/b978-1-4160-6645-3.00082-7
Khoshknabi, D. (2009) · Elsevier eBooks · doi:10.1016/b978-0-323-05674-8.50180-8
Spiegelhalder, K., Perlis, M. L., Hajak, G., & Riemann, D. W. (2009) · Elsevier eBooks · doi:10.1016/b978-3-437-24900-6.50020-4
Self-citationKapitel 15 – Schlafstörungen (ICD-10 F5)
Riemann, D., Spiegelhalder, K., Perlis, M. L., & Hajak, G. (2007) · Elsevier eBooks · doi:10.1016/b978-343724131-4.50019-6
Self-citation
Metadata
- 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 (medical) › 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
