Table 1.
Overview of literature cases of zolpidem abuse/misuse: summary of the main findings
| Study | Type of study (country) | Sample features (gender, age, psychiatric history) | Zolpidem (dosage, ROA) | Drugs/substances in combination (if any) | Clinical effects reported | Treatment |
|---|---|---|---|---|---|---|
| Bajaj et al. (2019) [65] | Case report (India) | n = 1, M, 45 yr, AUD | 2,400 mg/d, OS | Alcohol | Anxiolytic and anti-craving alcohol withdrawal | Propranolol (20−40 mg/d) |
| Kim et al. (2019) [38] | Case report (Korea) | n = 1, F, 69 yr, primary insomnia | 50−60 mg/d, OS | A liquid analgesic containing acetaminophen 200 mg, ethenzamide 100 mg, caffeine 30 mg and chlorpheniramine 2 mg | Aid to manage headache and insomnia | QUE (100 mg/d), melatonin (2 mg/d), acetaminophen (650 mg/d) |
| Lugoboni et al. (2019) [22] | Retrospective cohort study (Italy) | n = 107 (M = 51, F = 56); 44 ± 11 yr AUD (n = 15); OUD (n = 3), CoUD (n = 7); CUD (n = 3) |
NA for each patient; avail-able for 10 subjects (M = 8, F = 2); 10−1,800 mg/d, OS | BZDs, alcohol, methadone or other drugs of abuse (undefined number) | NA | NA |
| Sabe et al. (2019) [23] | Case report (Switzerland) | n = 1, F, 47 yr, insomnia secondary to ankylosing spondylitis | 120 mg/d, OS | Oxazepam | Irritability, aggressive behaviours, hypersexuality, disinhibition, megalomania and persecution delusions | HALO (5 mg im), LOR (2 mg im), OLA (10 mg/d), OXA(15 mg/d) |
| Chiaro et al. (2018) [52] | Case report (Switzerland) | n = 1, F, 70 yr, primary insomnia and PTSD | 1,200 mg/d, OS | None | Anxiolytic, relaxing effect, aid to coping stress related PTSD | SER (75 mg/d), CLO (2 mg/d), PRE (150 mg/d) |
| Ohshima et al. (2018) [39] | Case report (Japan) | n = 1, M, 29 yr, primary insomnia | 1,200 mg/d, OS | None | Anterograde amnesia, increased energy, sociable | Chlorpromazine (125 mg/d), CLO (6 mg/d) |
| Chattopadhyay et al. (2017) [36] | Case report (India) | n = 1, M, 33 yr, none | 1,700 mg/d, OS | Nicotine, quetiapine | Euphoria, ‘high’, sociable and talkative, nocturnal overeating | Unspecified |
| Majumder et al. (2017) [98] | Case report (India) | n = 1, M, 36 yr, MDD | 160−240 mg/d, OS | None | Euphoria | NA |
| Ahmadi (2016) [63] | Case report (Iran) | n = 1, M, 20 yr, substance- induced mood disorder | 100−200 mg/d, OS | Cannabis, alcohol | Aggressive behaviour, obsession, anxiety, depression after zol-pidem withdrawal | Unspecified |
| Haji Seyed Javadi et al. (2014) [91] | Case report (Iran) | n = 1, F, 30 yr, dysthymic disorder and chronic secondary insomnia | 100−150 mg/d, OS | None | Hyperactivity, increased energy, mood enhancement, seizure episode after zolpidem withdrawal | VEN (75 mg TID), CLO (1 mg/d), QUE (25 mg/d) |
| Mohapatra et al. (2014) [68] | Case report (India) | n = 1, M, 33 yr, none | 300 mg/d, OS | None | Enjoying the ‘high’ | NA |
| Pourshams and Malakouti (2014) [50] | Case report (Iran) | n = 1, F, 62 yr, MDD and OUD | 570 mg/d, OS | Opium combined with zolpidem (relaxing and euphoric effects) | Sleep, depressive and anxiety improvement | GABA (900 mg/d), SER (200 mg/d), TRA (100 mg/d) |
| Eslami- Shahrbabaki et al. (2014) [40] | Case report (Iran) | n = 1, M, 27 yr, schizophrenia and primary insomnia | 500 mg/d, OS | None | Social withdrawal, suspicious, aggressive behaviour, psychotic symptoms, hallucinations | RIS (2 mg TID), BIP (2 mg BID), TRA (100 mg/d) |
| Study | Type of study (country) | Sample features (gender, age, psychiatric history) | Zolpidem (dosage, ROA) | Drugs/substances in combination (if any) | Clinical effects reported | Treatment |
| Heydari and Isfeedvajani (2013) [67] | Case report (Iran) | n = 1, M, 32 yr, OUD | 1,110−1,400 mg/d, OS | Diphenoxylate | Euphoria, to manage tics | Unspecified |
| Fernandes et al. (2013) [49] | Case report (India) | n = 1, F, 72 yr, primary insomnia | 300 mg/d, OS | None | Diurnal sedation, mood swings, euphoria, dysphoria, increased energy | GABA (1,200 mg/d) |
| Liappas et al. (2013) [62] | Case series (Greece) | n = 3 A: M, 30 yr, CoUD |
A: 200−300 mg/d, OS | A: cocaine (3−4 g/d) | A: zolpidem as aid to manage co-caine craving, pathological gam-bler, hyperactive, excitement, childish behaviour, logorrhea, euphoria | A: FLU (20 mg BID) |
| B: F, 35 yr, onychophagia, ED and impulsive SA | B: 100−150 mg/d, OS | B: none | B: stimulant effect euphoria, mild dysarthria, hyperactivity, impul-sive behaviour, anterograde memory impairment | B: FLU (20 mg BID) | ||
| C: M, 42 yr, primary insomnia | C: 30−300 mg/day, OS | C: none | C: amnesia, memory blanks, con-fusion, energy to deal with his everyday problems, hyperac-tivity, euphoria | C: FLU (20 mg TID) | ||
| Chen et al. (2012) [92] | Case report (Taiwan) | n = 1, F, 53 yr, MDD | 100−160 mg/d, OS | None | Energy, daytime vitality, anxiety control | PAR (60 mg/d), FLUN (1 mg/d), QUE (200 mg/d) |
| Hsu and Chiu (2013) [97] | Case report (Taiwan) | n = 1, M, 29 yr, MDD and history of hypnotic abuse | 40 mg/d, IV | Not current | Dangerous driving, bizarre and impulsive behaviour | MIR (30 mg/d), oral zolpidem (20 mg/d) |
| Keuroghlian et al. (2012) [72] | Case report (USA) | n = 1, M, 34 yr, primary insomnia | 100−200 mg/d, OS | Alcohol | Grand mal seizure after zolpidem withdrawal | Chlordiazepoxide (unspecified dosage) |
| Kummer et al. (2012) [73] | Case report (Poland) | n = 2 A: F, 21 yr, primary insomnia B: F, 28 yr, primary insomnia |
10−15 mg/d, OS | Occasionally alcohol and cannabis | Pleasant visual (pseudo) halluci-nations, diplopia, mild agitation, logorrhea | Unspecified |
| Chien et al. (2011) [96] | Case report (Taiwan) | n = 1, M, 25 yr, MDD | 300−500 mg/d, OS | None | Helped against depression, euphoria | NA |
| Kinnan et al. (2011) [66] | Case report (USA) | n = 1, M, 27 yr, Schizoaffective disorder | 10 mg/d, OS | None | Baseline hypomania turned into a manic state | NA |
| Oulis et al. (2011) [88] | Case report (Greece) | n = 1, F, 49 yr, dysthymic disorder | 1,500 mg/d, OS | None | “Find relief from psychological difficulties”, “Gain strength in facing everyday professional and familial burdens” | PRE (450−900 mg/d) |
| Wang et al. (2011) [90] | Case report (Taiwan) | n = 2 A: F, 43 yr, dysthymic disorder |
A: 200−400 mg/d, OS | None | Euphoria, relaxing effect | A: LOR (2 mg/d), ALP (0.5 mg/d) |
| B: F, 35 yr, MDD | B: 400−500 mg/d, OS | B: CLO (unspecified dosage) | ||||
| Spyridi et al. (2009) [48] | Case report (NA) | n = 1, M, 78 yr, BZD dependence | 300 mg/d, OS | BZDs | Anxiolytic effect, energy | VA (unspecified dosage), MIR (unspecified dosage), QUE (unspecified dosage) |
| Case report (Greece) | n = 1, M, 78 yr, primary insomnia | 300 mg/d, OS | None | Euphoria, dysphoria, increased energy, insomnia | VA (1,000 mg/d), MIR (45 mg/d), QUE (100 mg/d) | |
| Jana et al. (2008) [61] | Case report (India) | n = 1, M, 33 yr, OUD | 100−150 mg/d, OS | None | Felt energic, active and happy | NA |
| Licata et al. (2008) [57] | Double-blind, placebo-con-trolled, cross over, pilot study (USA) | n = 7, F, 27 ± 5 yr, healthy | 10 mg/d, OS | None | Subjects effects characteristic of hypnotic drugs, reduced rating of drug ‘liking’, ‘willing to take again’, ‘willing to pay for’ vs. placebo | NA |
| Svitek et al. (2008) [56] | Case report (Germany) | n = 1, M, 27 yr, none | 800 mg/d, OS | None | Relaxed, pleasantly, stimulated and able to manage his daily activities | NA |
| Askew (2007) [100] | Case report (USA) | n = 1, F, 30 yr, pregnant, primary insomnia | 1,000 mg/d, OS | None | Not reported | Not reported |
| Benyamina et al. (2007) [60] | Case report (France) | n = 1, F, NA, SUD | 30−50 mg/4−5 times a week, IV | Alcohol, cannabis | Alcoholic inebriety, more powerful sensations, euphoria | PAR (40 mg/d) |
| Djezzar et al. (2006) [59] | Case report (France) | n = 1, M, 38 yr, OUD | 1,000 mg/d, OS | Dextromoramide | Euphoria, sensation of increased intellectual efficiency without dysphoric or sedative effect | NA |
| Quaglio et al. (2005) [55] | Case report (Italy) | n = 1, F, 39 yr, OCD, MDD | 400−800 mg/d, OS | None | Anxiolytic and euphoric effect | NA |
| Hill et al. (2004) [47] | Case report (USA) | n = 1, F, 67 yr, none | 10 mg/d | None | Manic state with insomnia and paranoid delusions | NA |
| Rappa et al. (2004) [89] | Case report (USA) | n = 1, M, 46 yr, stress-related insomnia | 400 mg/d, OS | Tramadol (100 mg QID) | “Cut some after-work anxieties” | DIA (10 mg/d), atenolol (25 mg/d), nefazodone (600 mg/d) |
| Liappas et al. (2003) [53] | Case series (Greece) | n = 8 A: F, 28 yr, dysthymic disorder |
A: 100−150 mg/d, OS | None but D (alcohol consumption), F (cannabis) | A: hyperactivity, euphoria, childish behaviour, anterograde memory impairment | A: not specified, drop-out |
| B: F, 35 yr, onychophagia, ED and impulsive SA | B: 100−150 mg/d, OS | B: hyperactivity, euphoria, impul-sive behaviour, anterograde memory impairment | B: FLU (20 mg BID) | |||
| C: M, 29 yr, avoidant personality disorder, anxious-depressive disorder | C: 100−300 mg/d, OS | C: hyperactivity, euphoria, impul-sive behaviour, anterograde memory impairment, irritability, dysarthria | C: VEN (75 mg BID) | |||
| D: F, 80 yr, anxious-depressive disorder and insomnia | D: 100 mg/d, OS | D: anxiolytic effect, compulsive zolpidem craving | D: not specified, relapse | |||
| E: F, 35 yr, primary insomnia and AUD | E: 450 mg/d, OS | E: mood enhancement, relaxing effect, sleep aid, anxiolytic effect | E: PAR (20 mg/d), clobazam (20 mg/d), propranolol (20 mg/d) | |||
| F: F, 33 yr, primary insomnia | F: 600 mg/d, OS | F: euphoria, self-confidence, sense of grandiosity, traffic accidents | F: not specified | |||
| G: F, 46 yr, dysthymic disorder, severe insomnia and BZD abuse | G: 200 mg/d, OS | G: anterograde memory impair-ment, confusion, mood eleva-tion | G: not specified, drop-out | |||
| H: F, 30 yr, dysthymic disorder | H: 300 mg/d, OS | H: stimulation, exaltation, epileptic seizures after abrupt disconti-nuation | H: not specified | |||
| Liappas et al. (2002) [58] | Case report (Greece) | n = 1, M, 30 yr, CoUD and secondary insomnia | 300 mg/d, OS | Cocaine | Euphoria, hyperactivity, childish behaviour, logorrhea, anti-craving cocaine | FLU (20 mg BID) |
| Madrak and Rosenberg (2001) [46] | Case report | n = 1, F, 67 yr, MDD | 100 mg/d, OS | Alcohol, barbiturate and BZD dependence | Unspecified | Chlordiazepoxide (300 mg/d) |
| Aragona (2000) [102] | Case report (Italy) | n = 1, F, 43 yr, primary insomnia | 450−600 mg/d, OS | None | Epileptic seizures after abrupt dis-continuation | Not reported |
| Golden and Vagnoni (2000) [70] | Case report (USA) | n = 1, M, 39 yr, primary insomnia | 40 mg/d, OS | Occasional alcohol consumption | Hyperactivity, increased alertness | Chlordiazepoxide (unspecified dosage) |
| Vartzopoulos et al. (2000) [71] | Case series (Greece) | n = 4 A: F, 42 yr, borderline person-ality disorder |
A: 300 mg/d, OS | A: BZD | A: anxiolytic effect | A: unspecified |
| B: F, 30 yr, histrionic personality disorder | B: 400−500 mg/d, OS | B: none | B: anxiolytic effect | B: unspecified | ||
| C: F, 26 yr, borderline person-ality disorder, AUD | C: 160−200 mg/d, OS | C: alcohol | C: anti-craving alcohol withdrawal, anxiolytic effect | C: unspecified | ||
| D: M, 33 yr, dysthymia, border-line personality disorder | D: 120 mg/d, OS | D: cannabis | D: relaxing and anxiolytic effect | D: unspecified | ||
| Ravishankar and Carnwath (1998) [103] | Case report (UK) | n = 2 A: NA, NA, MDD B: NA, NA, none |
A: 200 mg/d, OS B: 100 mg/d, OS |
NA | NA | NA |
| Gericke and Ludolph (1994) [95] | Case report (Germany) | n = 1, M, 33 yr, MDD | 280 mg/d, OS | None | Generalized tonic-clonic seizure, anterograde memory impairment | NA |
| Cavallaro et al. (1993) [45] | Case report (Italy) | n = 2 A: F, 60 yr, personality disorder |
A: 100 mg/d, OS | NA | A: dysarthria, confusion, disinhi-bition, anterograde amnesia; withdrawal syndrome described | A: IV chlordesmethyldiazepam (5 mg/d), flunitrazepam (20 mg/d), CLO (2 mg/d) |
| B: F, 31 yr, MDD | B: 80 mg/d, OS | B: withdrawal syndrome described | B: DIA (4 mg/d) | |||
| Sullivan et al. (1993) [69] | Case report (UK) | n = 1, M, 17 yr, NA | 450 mg/d, OS | Alcohol | Euphoria | Unspecified |
Values are presented as mean ± standard deviation.
ALP, alprazolam; AUD, Alcohol Use Disorder; BZDs, benzodiazepines; BID, two times daily; BIP, biperidene; CLO, clonazepam; CoUD, cocaine use disorder; CUD, cannabis use disorder; DIA, diazepam; ED, eating disorders; F, female; FLU, fluoxetine; FLUN, flunitrazepam; HALO, haloperidol; GABA, gabapentin; IV, intravenous; LOR, lorazepam; M, male; MDD, Major Depressive Disorder; MIR, mirtazapine; NA, not available; OCD, obsessive-compulsive disorder; OLA, olanzapine; OS, oral; OUD, opioid use disorder; OXA, oxazepam; PAR, paroxetine; PRE, pregabalin; QUE, quetiapine; RIS, risperidone; ROA, route of administration; SA, suicide attempt; SER, sertraline; SUD, substance use disorder; TID, three times daily; TRA, trazodone; VA, valproic acid; VEN, venlafaxine; PTSD, posttraumatic stress disorder; QID, quater in die.