zolpidem and Depression, Involutional studies

Zolpidem: An imidazopyridine derivative and short-acting GABA-A receptor agonist that is used for the treatment of INSOMNIA.
zolpidem : An imidazo[1,2-a]pyridine compound having a 4-tolyl group at the 2-position, an N,N-dimethylcarbamoylmethyl group at the 3-position and a methyl substituent at the 6-position.

Depression, Involutional: Form of depression in those MIDDLE AGE with feelings of ANXIETY.

Research Excerpts

Excerpt	Relevance	Reference
"REST-IT, a, 8-week double-blind RCT, compared zolpidem extended-release (ER) versus placebo at bedtime in 103 adults with major depressive disorder with insomnia and suicidal ideation, and who received open label selective serotonin reuptake inhibitors."	5.41	Blinding and bias in a hypnotic clinical trial. ( Benca, RM; Krystal, AD; McCall, WV; Rumble, ME, 2021)
"Individuals with major depressive disorder (MDD) often use hypnotics like zolpidem (Ambien(®)) to improve sleep in addition to their selective serotonin reuptake inhibitor (SSRI) regimen."	2.79	Zolpidem increases GABA in depressed volunteers maintained on SSRIs. ( Conn, NA; Jensen, JE; Licata, SC; Lukas, SE; Winer, JP, 2014)
"Chronic insomnia and depression are often associated."	2.74	Validation of the sleep impact scale in patients with major depressive disorder and insomnia. ( Crawford, B; Joish, VN; Lasch, K; Qiu, C; Rosa, K; Zhu, Y, 2009)
"In contrast, persistent insomnia measured both by the HRSD-17 insomnia subscale and the PSQI predicted recurrence."	2.73	Which symptoms predict recurrence of depression in women treated with maintenance interpersonal psychotherapy? ( Andreescu, C; Buysse, DJ; Cyranowski, JM; Dombrovski, AY; Frank, E; Houck, PR; Mallinger, AG; Mulsant, BH; Thase, ME, 2008)
"In continuation of a previous psychometric analysis of dose-response data for citalopram in depression, the corresponding study data for escitalopram is of interest, since escitalopram is the active enantiomer of citalopram and because citalopram was used as the active control."	2.71	Escitalopram dose-response revisited: an alternative psychometric approach to evaluate clinical effects of escitalopram compared to citalopram and placebo in patients with major depression. ( Andersen, HF; Bech, P; Cialdella, P; Pedersen, AG; Tanghøj, P, 2004)
" Approaches to the management of residual symptoms include addressing treatment-emergent side effects and co-morbid conditions, optimizing antidepressant dosing and using augmentation therapy."	2.43	Pharmacological approaches to the treatment of residual symptoms. ( Fava, M, 2006)
" We measured the risk of suicide/suicide attempt in association with zolpidem exposure by using adjusted odds ratios (ORs) and assessed the dose-response effect of zolpidem."	1.43	Association Between Zolpidem and Suicide: A Nationwide Population-Based Case-Control Study. ( Hsu, CY; Kao, CH; Lin, CC; Lu, CJ; Sun, Y, 2016)
"Zolpidem is a non-benzodiazepine hypnotic drug for treatment of insomnia."	1.40	Zolpidem abuse and dependency in an elderly patient with major depressive disorder: a case report. ( Malakouti, SK; Pourshams, M, 2014)
"Outpatients with borderline personality disorder (BPD) comprise up to 20% of psychiatry clinics, to which they are usually referred for treatment, not of their Axis II pathology but for comorbid Axis I conditions."	1.38	The challenge of treating (and supervising) patients with borderline pathology in a residents' clinic. ( Auchincloss, EL; Occhiogrosso, M, 2012)
"Zolpidem is a non-benzodiazepine property which binds selectively to the ?1-GABAA receptors, and has been widely prescribed to patients suffering from insomnia."	1.37	Zolpidem dependence and withdrawal seizure--report of two cases. ( Chu, CL; Juang, YY; Ree, SC; Wang, LJ, 2011)
"Although it has been claimed that insomnia causes an increased risk for depression, adequate controlled trials testing this hypothesis have not been available."	1.34	Greater incidence of depression with hypnotic use than with placebo. ( Kripke, DF, 2007)

Research

Studies (17)

Authors

Clinical Trials (3)

Trial Overview

Trial Outcomes

Actigraphy

Timeframe	Studies, this research(%)	All Research%
pre-1990	0 (0.00)	18.7374
1990's	1 (5.88)	18.2507
2000's	9 (52.94)	29.6817
2010's	6 (35.29)	24.3611
2020's	1 (5.88)	2.80

Authors	Studies
McCall, WV	1
Benca, RM	1
Rumble, ME	1
Krystal, AD	1
Pourshams, M	1
Malakouti, SK	1
Licata, SC	1
Jensen, JE	1
Conn, NA	1
Winer, JP	1
Lukas, SE	1
Sun, Y	1
Lin, CC	1
Lu, CJ	1
Hsu, CY	1
Kao, CH	1
Buysse, DJ	2
Dombrovski, AY	1
Cyranowski, JM	1
Mulsant, BH	1
Houck, PR	1
Andreescu, C	1
Thase, ME	1
Mallinger, AG	1
Frank, E	1
Hung, CI	1
Wang, SJ	1
Liu, CY	1
Lasch, K	1
Joish, VN	1
Zhu, Y	1
Rosa, K	1
Qiu, C	1
Crawford, B	1
Fava, M	2
Asnis, GM	1
Shrivastava, RK	1
Lydiard, B	1
Bastani, B	1
Sheehan, DV	1
Roth, T	1
Wang, LJ	1
Ree, SC	1
Chu, CL	1
Juang, YY	1
Occhiogrosso, M	1
Auchincloss, EL	1
Bech, P	1
Tanghøj, P	1
Cialdella, P	1
Andersen, HF	1
Pedersen, AG	1
Lange, CL	1
Kito, S	1
Koga, Y	1
Kripke, DF	1
Manciaux, MA	1
Tréchot, P	1
Hanesse, B	1
Cuny, G	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
Reducing Suicidal Ideation Through Insomnia Treatment[NCT01689909]	Phase 4	103 participants (Actual)	Interventional	2012-12-06	Completed
Maintenance Psychotherapies in Recurrent Depression: Study II[NCT00227981]		93 participants	Interventional	1995-03-31	Completed
Comparison of Zolpidem Tartrate Extended-Release vs. Placebo in Treatment of Insomnia Associated With Newly Diagnosed Major Depressive Disorder(MDD) or Untreated MDD Relapse, When Used Concomitantly With Escitalopram[NCT00296179]	Phase 4	372 participants	Interventional	2006-02-28	Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

"This device measures arm motion over time, reported as average actigraphic activity Level. The scale is reported as a continuous measure ranging from 0-200, and reported as the average score for each hour for all 24-hours of the day. Higher score represent greater c=activity at that point in time" (NCT01689909)
Timeframe: 8 weeks of treatment

Basis-32 - the Daily Living and Role Functioning (DLRF) Subscale

Intervention	units on a scale (Mean)
Scale for Suicide Ideation Score Greater Than or Equal to 6	150
Scale for Suicide Ideation Score Less Than 6	170

This is one of the subscales of the Basis 32. It is self-administered. This subscale has 7 items, each scored 0-4. The totals score is an average of the scores of these 7 items. Higher scores indicate more difficulty with daily living and role functioning. (NCT01689909)
Timeframe: 8 weeks of treatment

Beck Hopelessness Scale (BHS)

Intervention	units on a scale (Least Squares Mean)
Zolpidem-CR	1.51
Placebo	1.60

The Beck Hopelessness Scale is self administered and has 20 'true/false' choices. Some items are reversed scored. The range of scores for the total is 0-20, with higher scores indicating greater hopelessness (NCT01689909)
Timeframe: 8 weeks of treatment

Columbia Suicide Severity Rating Scale (C-SSRS): the Suicidal Ideation Scale

Intervention	units on a scale (Least Squares Mean)
Zolpidem-CR	9.40
Placebo	9.63

"The suicide ideation scale of the C-SSRS is rated 0-5, with 0 meaning no suicidal ideation, 1 meaning a wish t be dead, 2 meaning non-specific active suicidal thoughts, 3 meaning active suicidal ideation with any methods but no plan or intent, 4 meaning active suicidal ideation with some intent but no specific plan, and 5 meaning active suicidal ideation with intent and a specific plan" (NCT01689909)
Timeframe: 8 weeks of treatment

Disturbing Dreams and Nightmares Severity Index (DDNSI)

Intervention	units on a scale (Least Squares Mean)
Zolpidem-CR	0.5447
Placebo	0.8067

This self-rated scale has 5 items, with asymmetric weighting of each item. The range of the total score is 0-37, with higher scores indicating worse nightmares (NCT01689909)
Timeframe: 8 weeks of treatment

Dysfunctional Beliefs and Attitudes About Sleep

Intervention	units on a scale (Least Squares Mean)
Zolpidem-CR	5.74
Placebo	6.44

The Dysfunctional Beliefs and Attitudes About Sleep scale has 16 items and is self administered. Each item is scored 0-10. The total score is an average of the scores of the 16 items. Hence the range of the total score is also 0-10, with higher scores indicating greater dysfunctional beliefs about sleep (NCT01689909)
Timeframe: 8 weeks of treatment

Hamilton Rating Scale for Depression (HAM-D)

Intervention	units on a scale (Least Squares Mean)
Zolpidem-CR	6.03
Placebo	6.07

This version of the Hamilton Rating Scale for Depression uses 24 items, with a possible total score ranging from 0-74, with higher scores indicating worse depression (NCT01689909)
Timeframe: 8 weeks of treatment

Insomnia Severity Index (ISI)

Intervention	units on a scale (Least Squares Mean)
Zolpidem-CR	14.93
Placebo	15.89

The Insomnia Severity Index is self rated. It has 7 items, each scored 0-4. Therefore the range of scores is 0-28, with higher scores indicating worse insomnia (NCT01689909)
Timeframe: 8 weeks of treatment

Scale for Suicide Ideation Index (SSI)

Intervention	units on a scale (Least Squares Mean)
Zolpidem-CR	11.28
Placebo	13.72

This is the total score for the Scale for Suicide Ideation. It has 19 items, each scored 0-2, for a maximum of 38 points. Higher scores indicate worse suicidal ideation (NCT01689909)
Timeframe: Over 8 weeks of treatment

Article	Year
Blinding and bias in a hypnotic clinical trial. Human psychopharmacology, 2021, Volume: 36, Issue:1 Topics: Adolescent; Adult; Bias; Depressive Disorder, Major; Double-Blind Method; Female; Humans; Hypnotics	2021
Zolpidem increases GABA in depressed volunteers maintained on SSRIs. Psychiatry research, 2014, Oct-30, Volume: 224, Issue:1 Topics: Adult; Depressive Disorder, Major; Female; GABA-A Receptor Agonists; gamma-Aminobutyric Acid; Humans	2014
Which symptoms predict recurrence of depression in women treated with maintenance interpersonal psychotherapy? Depression and anxiety, 2008, Volume: 25, Issue:12 Topics: Adult; Affect; Anxiety Disorders; Combined Modality Therapy; Comorbidity; Depressive Disorder, Major	2008
Validation of the sleep impact scale in patients with major depressive disorder and insomnia. Current medical research and opinion, 2009, Volume: 25, Issue:7 Topics: Adult; Aged; Antidepressive Agents; Citalopram; Delayed-Action Preparations; Depressive Disorder, Ma	2009
Improved insomnia symptoms and sleep-related next-day functioning in patients with comorbid major depressive disorder and insomnia following concomitant zolpidem extended-release 12.5 mg and escitalopram treatment: a randomized controlled trial. The Journal of clinical psychiatry, 2011, Volume: 72, Issue:7 Topics: Adult; Antidepressive Agents, Second-Generation; Citalopram; Delayed-Action Preparations; Depressive	2011
Escitalopram dose-response revisited: an alternative psychometric approach to evaluate clinical effects of escitalopram compared to citalopram and placebo in patients with major depression. The international journal of neuropsychopharmacology, 2004, Volume: 7, Issue:3 Topics: Antidepressive Agents; Citalopram; Depressive Disorder, Major; Dose-Response Relationship, Drug; Dou	2004

Article	Year
Zolpidem abuse and dependency in an elderly patient with major depressive disorder: a case report. Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences, 2014, Jul-10, Volume: 22 Topics: Depressive Disorder, Major; Female; Humans; Hypnotics and Sedatives; Middle Aged; Narcotics; Opium;	2014
Association Between Zolpidem and Suicide: A Nationwide Population-Based Case-Control Study. Mayo Clinic proceedings, 2016, Volume: 91, Issue:3 Topics: Adult; Age Factors; Antidepressive Agents; Case-Control Studies; Comorbidity; Depressive Disorder, M	2016
Chronic insomnia. The American journal of psychiatry, 2008, Volume: 165, Issue:6 Topics: Adult; Behavior Therapy; Chronic Disease; Combined Modality Therapy; Comorbidity; Depressive Disorde	2008
Validation of the Depression and Somatic Symptoms Scale by comparison with the Short Form 36 scale among psychiatric outpatients with major depressive disorder. Depression and anxiety, 2009, Volume: 26, Issue:6 Topics: Adolescent; Adult; Ambulatory Care; Antidepressive Agents, Second-Generation; Cyclohexanols; Delayed	2009
Zolpidem dependence and withdrawal seizure--report of two cases. Psychiatria Danubina, 2011, Volume: 23, Issue:1 Topics: Adult; Cerebral Cortex; Comorbidity; Depressive Disorder, Major; Dose-Response Relationship, Drug; D	2011
The challenge of treating (and supervising) patients with borderline pathology in a residents' clinic. Psychodynamic psychiatry, 2012, Volume: 40, Issue:3 Topics: Adult; Antidepressive Agents, Second-Generation; Borderline Personality Disorder; Countertransferenc	2012
Medication-associated somnambulism. Journal of the American Academy of Child and Adolescent Psychiatry, 2005, Volume: 44, Issue:3 Topics: Adolescent; Cyclohexanols; Depressive Disorder, Major; Female; Humans; Hypnotics and Sedatives; Pyri	2005
Visual hallucinations and amnesia associated with zolpidem triggered by fluvoxamine: a possible interaction. International psychogeriatrics, 2006, Volume: 18, Issue:4 Topics: Aged, 80 and over; Amnesia; Antidepressive Agents, Second-Generation; Depressive Disorder, Major; Do	2006
Greater incidence of depression with hypnotic use than with placebo. BMC psychiatry, 2007, Aug-21, Volume: 7 Topics: Acetamides; Azabicyclo Compounds; Cross-Sectional Studies; Depressive Disorder, Major; Drug Prescrip	2007
[Unexpected beneficial effect of the ingestion of zolpidem (Stilnox)]. La Revue de medecine interne, 1993, Volume: 14, Issue:1 Topics: Aged; Depressive Disorder, Major; Female; Humans; Hypnotics and Sedatives; Pyridines; Zolpidem	1993

zolpidem and Depression, Involutional