4.2. Analysis.
Comparison 4 Bupropion and nortriptyline. Adverse events, Outcome 2 Bupropion versus control. 'No report' = no information, 'None occurred' = explicit statement.
| Bupropion versus control. 'No report' = no information, 'None occurred' = explicit statement | |||
|---|---|---|---|
| Study | Serious events | Other adverse events | Withdrawal due to AE |
| Ahluwalia 2002 | No seizures occurred No serious adverse events reported. | Insomnia (29.3 vs 20.7%) more common with bupropion. Dry mouth (28% vs 24%) | No information |
| Aubin 2004 | No seizures occurred 5 bupropion and 1 placebo serious AE during treatment, 2 bupropion during f‐up. 1 chest pain, tremor & sweating & 1 depressive syndrome after end of treatment considered possibly due to bupropion. | 61% on bupropion and 45% on placebo experienced at least one AE Sleep disorder 33% bupropion vs 19% placebo | 10% bupropion & 5% placebo withdrew due to AEs |
| Cinciripini 2013 | No seizures occurred 3 SAEs (within 30 days of treatment) in bupropion group: bilateral mammoplasty, facial paralysis and syncope. 2 SAEs in placebo group: diabetes mellitus and chest pain. |
Significantly higher rates of influenza (7.8% vs 1.9%), nausea (16.7% vs 7.5%) and insomnia (31.4% vs 19.8%) in bupropion than placebo group. Significantly less diarrhoea in intervention than control group (11.3 vs 3.9%). No other significant differences detected. | 2% bupropion and 1% placebo withdrew due to AEs |
| Collins 2004 | Not reported in paper | Not reported in paper | Not reported in paper |
| Covey 2007 | One seizure during open label phase (before randomization to relapse prevention) | 'The number of reported side effects (e.g. nervousness, constipation, insomnia, stomach‐ache, depressed mood) was low (mean = 0.43, SD = 0.91), and did not vary by treatment group (P = 0.69)' | None reported |
| Cox 2012 | None occurred in first 3 weeks of treatment (not reported beyond that) | Type of AE not reported. All AEs in first week of treatment 8.9% bupropion and 28.5% placebo group. | Not reported in paper |
| Dalsgarð 2004 | No seizures occurred No serious adverse event during treatment phase. 3 events during follow‐up not considered to be drug related including 1 death in bupropion group, | Insomnia (28% vs 18%), dizziness (8% vs 1%) and skin problems (15% vs 7%) significantly more common with bupropion. Major depression more common in placebo (1% vs 5%), | 12% bupropion & 8% placebo withdrew due to adverse event. |
| Eisenberg 2013 | No seizures occurred. Over the course of 12 months, 17.7% bupropion and 18.5% placebo experienced SAE. No SAEs considered related to treatment. | Over course of study treatment, no significant difference in AEs. Most common were insomnia (22.3% bupropion vs 18.2% placebo), dry mouth (13.3% bupropion vs 9.1% placebo), and dizziness (8.0% bupropion vs 8.6% placebo). | Not reported |
| Evins 2001 | No seizures occurred | No information (only 19 participants) | No information |
| Evins 2005 | Not reported in abstract | Not reported in abstract | Not reported in abstract |
| Ferry 1992 | No seizures occurred (data from FDA submission) | No information from abstract | No information from abstract |
| Ferry 1994 | No seizures occurred (data from FDA submission) | No information from abstract | 3% bupropion & 3% placebo withdrew due to adverse experience (data from FDA submission) |
| Fossati 2007 | No seizures occurred 8 serious adverse events in bupropion group, of which 1 thought to be medication related (suspected cholangitis) | Dry mouth (6.3% vs 2.1%), Insomnia (17.3% vs 6.2%), and constipation (11.0% vs 3.6%) significantly more common on bupropion | ˜14% bupropion & 7% placebo withdrew due to AEs |
| George 2002 | No seizures occurred | Dry mouth (62.5% vs 25.0%) , headache (56.3% vs 37.5%), insomnia (43.8% vs 27.8%), memory problems (50.0% vs 31.3%), blurred vision (50.0% vs 25.0%, irregular heartbeat (37.5% vs 12.5%), nausea/vomiting (43.8% vs 18.8%) diarrhoea (50.0% vs 25.0%), anxiety/agitation (50.0% vs 25.0%), tremor (31.3% vs 12.5%) | 2 bupropion & 5 placebo withdrew during treatment, no reasons given |
| George 2008 | No seizures occurred. Three serious adverse events (SAEs) involved psychotic decompensation, 2 placebo, 1 bupropion. All deemed unrelated to study medications | There were significant (p <.05) group differences on concentration, jitteriness, lightheadedness, muscle stiffness, and frequent nocturnal awakening | No information on AE related withdrawals |
| Gonzales 2001 | No seizures occurred. One serious adverse event (rash with pruritus and edema) in the bupropion group was assessed as being due to study medication | No significant differences between bupropion & placebo. 72% on bupropion reported adverse event vs 58% placebo. Most common adverse events insomnia (24% vs 11%), viral infections (13% vs 19%) dry mouth (13% vs 9%), headache (8% vs 13%), | 30 people discontinued medication due to adverse event, 11 (5%) placebo, 19 (8%) bupropion. For patients on bupropion most common events were anxiety (4), dry mouth (3) and rash (3) |
| Gonzales 2006 | 1 seizure after 20 days of bupropion. No other serious events assessed as due to medication | Dry mouth (8.8% vs 5.5%, NS), nausea (12.5% vs 8.4%, NS), insomnia (21.9% vs 12.8%) | 9.0% placebo, 15.2% bupropion discontinued medication |
| Grant 2007 | No seizures occurred | Insomnia (37% vs 7%) | 10 (33%) discontinued bupropion vs 3 (11%) placebo |
| Haggsträm 2006 | No seizures or other serious adverse events occurred | Insomnia (50.9% vs 17.6%), dry mouth (50.9% vs 31.4%), diarrhoea (11.0% vs 3.9%) | No report |
| Hall 2002 | No seizures occurred | No significant differences between bupropion & placebo | No report |
| Hatsukami 2004 | No seizures occurred. 8 serious AEs in bupropion, 3 placebo. One case of chest pain thought to be treatment related. | No details | 60 people discontinued medication due to adverse events, 22 (7%) placebo, 38 (13%) bupropion. |
| Hays 2001 | No seizures occurred. No serious adverse events assessed as being caused by study medication | No significant differences between bupropion and placebo. Most common adverse events during 45 week double blind medication phase insomnia (10% vs 7%) and headache (24% vs 17%) also rhinitis, influenza URI and accidental injury. | 41 people discontinued medication due to adverse events, 17 (8%) placebo, 24 (11%) bupropion. |
| Hertzberg 2001 | No seizures occurred. One patient receiving bupropion suffered ataxia, headache and jitteriness. | No details | One bupropion (ataxia, headache and jitteriness) |
| Holt 2005 | No seizures or serious adverse events | Insomnia 26% vs 9% | Three discontinued bupropion due to a rash. |
| Hurt 1997 | No seizures occurred. One of three serious adverse events could have been associated with bupropion; extreme irritability restlessness, anger, anxiety and craving in a man who stopped smoking. | Bupropion 300mg was associated with significantly more insomnia (34.6% vs 20.9%) and dry mouth (12.8% vs 4.6%) than placebo. | 37 people discontinued medication due to adverse events; 6 (5%) placebo; 9 (6%) 100mg; 7 (5%) 150mg; 13 (8%) 300mg. Tremor, headaches, rash and urticaria were the most common reasons for stopping treatment. |
| Hurt 2003 | No seizures occurred | No significant differences. Anxiety (16% vs 9%) and nervousness (13% vs 6%) more common in bupropion group. Insomnia less common (10% vs 17%). | Not stated. |
| Jorenby 1999 | No seizures occurred. Three serious adverse events were attributed to bupropion, all consisted of rash and pruritus, one with shortness of breath and chest tightness. All had full resolution of symptoms | Bupropion was associated with more insomnia (42.4% vs 19.5%) and dry mouth (10.7% vs 4.4%) than placebo. | 79 people discontinued medication due to adverse events; 6 (3.8%) placebo; 16 (6.6%) patch; 29 (11.9%) bupropion and 28 (11.4%) combined treatment group. 20% dropped out of study, and 35% were lost to follow‐up at 12 months. |
| Jorenby 2006 | No seizures occurred 1 serious adverse event attributed to bupropion; angioedema. | Bupropion was associated with more insomnia (21.2% vs 12.4%), sleep disorder (6.8% vs 2.6%), constipation (6.5% vs 1.5%), dry mouth (7.6% vs 3.2%). | 16 (4.7%) bupropion vs 13 (3.8%) placebo discontinued study due to AEs. 12.6% vs 7.3% discontinued medication. |
| Killen 2004 | No seizures occurred. No adverse effects judged to be severe by study physician | 22 (21%) reported severe AEs in bupropion & patch group vs 25 (23%) in placebo & patch. 24 (23%) vs 35 (32%) reported moderate AEs | None reported |
| Killen 2006 | 1 seizure during open‐label phase 2 other serious adverse events during open label phase (oedema, depression) and 2 during extended treatment (diagnosis of hyperthyroidism in bupropion group, onset of immune thrombocytopenia purpura in placebo group). | During open‐label phase 53% reported insomnia, 47% dry mouth, 44% vivid dreams, 23% nausea, 22% headache, 17% racing heart rate, 12% skin rash and 7% irregular heart rate. | 30 (8%) discontinued medication during open‐label phase. 1 bupropion and 2 placebo discontinued during extended treatment phase. |
| Levine 2010 | "No serious events were associated with medication use." No further information reported. | "Overall, bupropion was well tolerated." No further detail provided. | "Reasons for medication discontinuation did not differ between bupropion and placebo, with the exception of allergic reaction (5.64% vs 0.65% in bupropion vs placebo, p = 0.02). No further detail provided. |
| Muramoto 2007 | No seizures occurred. 1 hospitalisation (150 mg/d group) for deliberate ingestion of Datura innoxia for recreational purposes. 1 hospitalisation (150 mg/d group) for intentional overdose of study medication, other drugs & alcohol. | Headache and cough were commonest reported AEs. No others significantly different. | Eight subjects discontinued medication early because of the following adverse events: feeling depressed, irritable, or angry; sleep disturbance; headache; urticaria; anxiety; heart palpitations; suicide attempt; anticholinergic crisis related to recreational drug use; and pregnancy. |
| Nides 2006 | Two seizures, 2 other serious AEs in bupropion (persistent intermittent bloody diarrhoea, syncope) all considered to be possibly related to bupropion | 90% of bupropion and 88% on placebo experienced at least one AE. Insomnia 45% bupropion vs 22% placebo, constipation 14% bupropion vs 4% placebo, dry mouth 12% bupropion vs 6% placebo. | 16% bupropion & 10% placebo discontinued medication |
| Piper 2007 | No report of seizures | 4.7% of adverse events was insomnia, not reported by condition | Not reported |
| Piper 2009 | 1 seizure in bupropion group, but other SAEs not reported | In bupropion vs placebo, more diarrhea (1.5% vs 1.1%), vomiting (1.9% vs 1.1%), dry mouth (3.8% vs 1.0%), and sleep disturbance and abnormal dreams (16.8% vs 5.6%). In all other AEs, same or more occurred in placebo arm. | 2 in bupropion group withdrew because of events related to medication (1 interaction related to other antidepressants; 1 heartburn). 1 placebo withdrew because of "negative experience" whilst on medication. |
| Planer 2011 | Over course of one year, 3% bupropion and 1% placebo MI, 3% bupropion and 7% placebo ACS. | No significant differences in any AEs over one year except for increased rate of dizziness in bupropion users (14% bupropion vs 1.4% placebo) | Not reported |
| Rigotti 2006 | No report of seizures. Two deaths in placebo group. Non cardiac serious adverse events; 37% bupropion vs 31% placebo, ns Rate of new cardiovascular events did not differ significantly at 3 months or 1 year. After 30 days off drug more bupropion group sustained a cardiovascular event, borderline significance after adjustment for cardiac risk factors. | Not reported | Withdrawals not reported |
| Rovina 2009 | No seizures in either two arms included in this analysis. 0.9% tachycardia in bupropion arm vs 0 in control arm during 19 weeks of treatment. | Higher rates in bupropion than in control arm of: insomnia (15.8% vs 3.2%), dry mouth (12.9% vs 0), dizziness (8.8% vs 0), constipation (5.5% vs 1.2%), headache (5.8% vs 4.5%), anxiety (4.8% vs 3.7%), nausea (5% vs 0), concentration issues (4.2% vs 1.2%), allergic reaction (5.8% vs 0), sadness (2.6% vs 0.4%), and sleepiness (1.4% vs 0). | Not reported |
| Simon 2004 | No report of seizures or other serious AE | Frequency of insomnia and abnormal dreams similar in both groups. Dry mouth 22% bupropion vs 8% placebo, gastrointestinal upset 9% bupropion vs 1% placebo | Withdrawals not reported |
| Simon 2009 | No seizures occurred. 1 death in each group, causes not given (hospital population) | 11 (26%) bupropion vs 4 (9%) in the placebo reported any AEs. Hyperactivity and insomnia reported solely in bupropion group | Not reported |
| SMK20001 | No seizures or deaths occurred. 7 patients (bupropion 4, placebo 3) experienced a serious AE, none considered related to medication. | Overall rate of reporting of adverse events 90% vs 83%. Sleep disorders 46% vs 27% | 7% vs 1% withdrew due to AEs |
| Stapleton 2013 | No seizures occurred. 4 patients receiving bupropion had an SAE whilst on treatment (2 allergic reactions resulting in anaphylaxis, 1 transient suicidal thoughts, 1 severe chest pain). No SAEs occured in group receiving NRT only. | Higher rates of some adverse events in participants receiving bupropion compared to those receiving NRT only: disturbed sleep, dry mouth, headache, nausea, dizziness, low mood/depression, anxiety/panic, chest pain, disorientation, loss of appetite. | 20% of abstinent participants allocated to bupropion only had switched to NRT. No further detail reported on withdrawal due to AEs. |
| Swan 2003 | No seizures or deaths occurred. No serious AEs reported | Higher dose associated with more difficulty sleeping (48% vs 41%), difficulty concentrating (35% vs 28%), gastrointestinal problems (27% vs 20%) and shakiness/tremor (24% vs 17%) than lower dose. | 26% discontinued medication in 150 mg group and 31% in 300 mg group |
| Tashkin 2001 | No seizures occurred. 6 patients (placebo 5, bupropion 1) experienced a serious adverse event. One event (transient ischaemic attack) in placebo group thought to be related to study treatment. | Bupropion associated with more insomnia (24% vs 12%). Rates for headache (6% vs 6%) and dry mouth (6% vs 5%) similar in 2 groups. | 27 people discontinued medication, bupropion 14 (7%), placebo 13 (6.5%). Commonest reasons in bupropion group were anxiety (5), insomnia (4) |
| Tonnesen 2003 | No seizures occurred 7 patients (bupropion 6, placebo 1) experienced serious AEs within a week of ending treatment. A reasonable possibility that SAEs in 3 bupropion patients related to study medication (fainting due to insomnia, urticaria/angioedema (2). In addition one bupropion patient delivered twin girls 4 weeks after treatment termination, one still born. | Bupropion associated with more insomnia (24% vs 15%), dry mouth (13% vs 5%) headache (13% vs 10%) sleep disorder (10% vs 7%), constipation (6% vs 1%) and dizziness (7% vs 4%) | 8% on bupropion and 6% on placebo withdrew due to adverse events. |
| Tonstad 2003 | No seizures occurred. Five serious adverse events during treatment, all on bupropion. Only 1 (lupus disseminatus) considered related to medication. None led to medication discontinuation. Three SAEs within a week of treatment, none related to bupropion use. 36 patients (Bupropion 24, placebo 14) reported cardiovascular adverse events. 4 deaths (2, 2) during follow‐up phase, none related to study medication. | Bupropion associated with more insomnia (24% vs 12%), dry mouth (18% vs 10%), nausea (13% vs 6%), dizziness (8% vs 5%). 11% in each group reported headache. No evidence of any effect on vital signs in CVD patients. | 5% on bupropion and 6% on placebo withdrew due to adverse events. |
| Uyar 2007 | No seizures occurred | 56% on bupropion reported dry mouth, 44% headache, 40% insomnia. Sleep disturbance rates significantly higher than control (38% vs 9.6%). | 4 (8%) discontinued bupropion due to adverse effects |
| Wagena 2005 | No seizures occurred One death in placebo group, previously hospitalised with dermatological reactions | No significant differences between bupropion & placebo. Insomnia 34% vs 24%, Dry mouth 28% vs 20%, diarrhoea or constipation 34% vs 26% | 15% on bupropion and 9% on placebo discontinued medication |
| Wittchen 2011 | None occurred | Insomnia (7%) and dry mouth (7%) most frequently reported in bupropion group, rates not given for control group | 7 on bupropion discontinued due to adverse effects (11 in NRT group, 0 in control group) |
| Zellweger 2005 | Two seizures occurred in bupropion group. One patient had a possible familial predisposition and the other was sleep deprived. 1 patient on placebo suffered a transient ischemic attack and 1 a pulmonary sequestration | Bupropion associated with more insomnia (39% vs 22%). Similar rates of dry mouth (12% vs 10%), agitation (10% vs 11%), nausea (10% vs 7%). | 9% on bupropion and 5% on placebo withdrew due to adverse events, most commonly due to nervous system events in both groups. |