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Acta Psychiatrica Scandinavica Jul 2021Narcolepsy is a rare sleep disorder in which psychotic-like symptoms can present diagnostic and therapeutic challenges. We aimed to review the association between, and... (Review)
Review
OBJECTIVE
Narcolepsy is a rare sleep disorder in which psychotic-like symptoms can present diagnostic and therapeutic challenges. We aimed to review the association between, and medical management of, narcolepsy and psychosis in children and adults.
METHODS
We reviewed the full text of 100 papers from 187 identified by a PubMed search on narcolepsy plus any of these keywords: psychosis, schizophrenia, delusion, side effects, safety, and bipolar disorder.
RESULTS
Three relevant groups are described. (i) In typical narcolepsy, psychotic-like symptoms include predominantly visual hallucinations at the sleep-wake transition (experienced as "not real") and dissociation because of intrusion of rapid eye movement (REM) sleep phenomena into wakefulness. (ii) Atypical patients ("the psychotic form of narcolepsy") experience more severe and vivid, apparently REM-related hallucinations or dream/reality confusions, which patients may rationalize in a delusion-like way. (iii) Some patients have a comorbid schizophrenia spectrum disorder with psychotic symptoms unrelated to sleep. Psychostimulants used to treat narcolepsy may trigger psychotic symptoms in all three groups. We analyzed 58 published cases from groups 2 and 3 (n = 17 and 41). Features that were reported significantly more frequently in atypical patients include visual and multimodal hallucinations, sexual and mystical delusions, and false memories. Dual diagnosis patients had more disorganized symptoms and earlier onset of narcolepsy.
CONCLUSION
Epidemiological studies tentatively suggest a possible association between narcolepsy and schizophrenia only for very early-onset cases, which could be related to the partially overlapping neurodevelopmental changes observed in these disorders. We propose a clinical algorithm for the management of cases with psychotic-like or psychotic features.
Topics: Adult; Child; Hallucinations; Humans; Narcolepsy; Psychotic Disorders; Schizophrenia; Sleep, REM
PubMed: 33779983
DOI: 10.1111/acps.13300 -
The Cochrane Database of Systematic... Jul 2022Schizophrenia is a disabling psychotic disorder characterised by positive symptoms of delusions, hallucinations, disorganised speech and behaviour; and negative symptoms... (Review)
Review
BACKGROUND
Schizophrenia is a disabling psychotic disorder characterised by positive symptoms of delusions, hallucinations, disorganised speech and behaviour; and negative symptoms such as affective flattening and lack of motivation. Cognitive behavioural therapy (CBT) is a psychological intervention that aims to change the way in which a person interprets and evaluates their experiences, helping them to identify and link feelings and patterns of thinking that underpin distress. CBT models targeting symptoms of psychosis (CBTp) have been developed for many mental health conditions including schizophrenia. CBTp has been suggested as a useful add-on therapy to medication for people with schizophrenia. While CBT for people with schizophrenia was mainly developed as an individual treatment, it is expensive and a group approach may be more cost-effective. Group CBTp can be defined as a group intervention targeting psychotic symptoms, based on the cognitive behavioural model. In group CBTp, people work collaboratively on coping with distressing hallucinations, analysing evidence for their delusions, and developing problem-solving and social skills. However, the evidence for effectiveness is far from conclusive.
OBJECTIVES
To investigate efficacy and acceptability of group CBT applied to psychosis compared with standard care or other psychosocial interventions, for people with schizophrenia or schizoaffective disorder.
SEARCH METHODS
On 10 February 2021, we searched the Cochrane Schizophrenia Group's Study-Based Register of Trials, which is based on CENTRAL, MEDLINE, Embase, four other databases and two trials registries. We handsearched the reference lists of relevant papers and previous systematic reviews and contacted experts in the field for supplemental data.
SELECTION CRITERIA
We selected randomised controlled trials allocating adults with schizophrenia to receive either group CBT for schizophrenia, compared with standard care, or any other psychosocial intervention (group or individual).
DATA COLLECTION AND ANALYSIS
We complied with Cochrane recommended standard of conduct for data screening and collection. Where possible, we calculated risk ratio (RR) and 95% confidence interval (CI) for binary data and mean difference (MD) and 95% CI for continuous data. We used a random-effects model for analyses. We assessed risk of bias for included studies and created a summary of findings table using GRADE.
MAIN RESULTS
The review includes 24 studies (1900 participants). All studies compared group CBTp with treatments that a person with schizophrenia would normally receive in a standard mental health service (standard care) or any other psychosocial intervention (group or individual). None of the studies compared group CBTp with individual CBTp. Overall risk of bias within the trials was moderate to low. We found no studies reporting data for our primary outcome of clinically important change. With regard to numbers of participants leaving the study early, group CBTp has little or no effect compared to standard care or other psychosocial interventions (RR 1.22, 95% CI 0.94 to 1.59; studies = 13, participants = 1267; I = 9%; low-certainty evidence). Group CBTp may have some advantage over standard care or other psychosocial interventions for overall mental state at the end of treatment for endpoint scores on the Positive and Negative Syndrome Scale (PANSS) total (MD -3.73, 95% CI -4.63 to -2.83; studies = 12, participants = 1036; I = 5%; low-certainty evidence). Group CBTp seems to have little or no effect on PANSS positive symptoms (MD -0.45, 95% CI -1.30 to 0.40; studies =8, participants = 539; I = 0%) and on PANSS negative symptoms scores at the end of treatment (MD -0.73, 95% CI -1.68 to 0.21; studies = 9, participants = 768; I = 65%). Group CBTp seems to have an advantage over standard care or other psychosocial interventions on global functioning measured by Global Assessment of Functioning (GAF; MD -3.61, 95% CI -6.37 to -0.84; studies = 5, participants = 254; I = 0%; moderate-certainty evidence), Personal and Social Performance Scale (PSP; MD 3.30, 95% CI 2.00 to 4.60; studies = 1, participants = 100), and Social Disability Screening Schedule (SDSS; MD -1.27, 95% CI -2.46 to -0.08; studies = 1, participants = 116). Service use data were equivocal with no real differences between treatment groups for number of participants hospitalised (RR 0.78, 95% CI 0.38 to 1.60; studies = 3, participants = 235; I = 34%). There was no clear difference between group CBTp and standard care or other psychosocial interventions endpoint scores on depression and quality of life outcomes, except for quality of life measured by World Health Organization Quality of Life Assessment Instrument (WHOQOL-BREF) Psychological domain subscale (MD -4.64, 95% CI -9.04 to -0.24; studies = 2, participants = 132; I = 77%). The studies did not report relapse or adverse effects.
AUTHORS' CONCLUSIONS
Group CBTp appears to be no better or worse than standard care or other psychosocial interventions for people with schizophrenia in terms of leaving the study early, service use and general quality of life. Group CBTp seems to be more effective than standard care or other psychosocial interventions on overall mental state and global functioning scores. These results may not be widely applicable as each study had a low sample size. Therefore, no firm conclusions concerning the efficacy of group CBTp for people with schizophrenia can currently be made. More high-quality research, reporting useable and relevant data is needed.
Topics: Adult; Cognitive Behavioral Therapy; Hallucinations; Humans; Psychotic Disorders; Quality of Life; Schizophrenia
PubMed: 35866377
DOI: 10.1002/14651858.CD009608.pub2 -
The Cochrane Database of Systematic... Nov 2022Perception is the ability to understand information from our senses. It allows us to experience and meaningfully interact with our environment. A stroke may impair... (Review)
Review
BACKGROUND
Perception is the ability to understand information from our senses. It allows us to experience and meaningfully interact with our environment. A stroke may impair perception in up to 70% of stroke survivors, leading to distress, increased dependence on others, and poorer quality of life. Interventions to address perceptual disorders may include assessment and screening, rehabilitation, non-invasive brain stimulation, pharmacological and surgical approaches.
OBJECTIVES
To assess the effectiveness of interventions aimed at perceptual disorders after stroke compared to no intervention or control (placebo, standard care, attention control), on measures of performance in activities of daily living. SEARCH METHODS: We searched the trials registers of the Cochrane Stroke Group, CENTRAL, MEDLINE, Embase, and three other databases to August 2021. We also searched trials and research registers, reference lists of studies, handsearched journals, and contacted authors.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) of adult stroke survivors with perceptual disorders. We defined perception as the specific mental functions of recognising and interpreting sensory stimuli and included hearing, taste, touch, smell, somatosensation, and vision. Our definition of perception excluded visual field deficits, neglect/inattention, and pain.
DATA COLLECTION AND ANALYSIS
One review author assessed titles, with two review authors independently screening abstracts and full-text articles for eligibility. One review author extracted, appraised, and entered data, which were checked by a second author. We assessed risk of bias (ROB) using the ROB-1 tool, and quality of evidence using GRADE. A stakeholder group, comprising stroke survivors, carers, and healthcare professionals, was involved in this review update.
MAIN RESULTS
We identified 18 eligible RCTs involving 541 participants. The trials addressed touch (three trials, 70 participants), somatosensory (seven trials, 196 participants) and visual perception disorders (seven trials, 225 participants), with one (50 participants) exploring mixed touch-somatosensory disorders. None addressed stroke-related hearing, taste, or smell perception disorders. All but one examined the effectiveness of rehabilitation interventions; the exception evaluated non-invasive brain stimulation. For our main comparison of active intervention versus no treatment or control, one trial reported our primary outcome of performance in activities of daily living (ADL): Somatosensory disorders: one trial (24 participants) compared an intervention with a control intervention and reported an ADL measure. Touch perception disorder: no trials measuring ADL compared an intervention with no treatment or with a control intervention. Visual perception disorders: no trials measuring ADL compared an intervention with no treatment or control. In addition, six trials reported ADL outcomes in a comparison of active intervention versus active intervention, relating to somatosensation (three trials), touch (one trial) and vision (two trials). AUTHORS' CONCLUSIONS: Following a detailed, systematic search, we identified limited RCT evidence of the effectiveness of interventions for perceptual disorders following stroke. There is insufficient evidence to support or refute the suggestion that perceptual interventions are effective. More high-quality trials of interventions for perceptual disorders in stroke are needed. They should recruit sufficient participant numbers, include a 'usual care' comparison, and measure longer-term functional outcomes, at time points beyond the initial intervention period. People with impaired perception following a stroke should continue to receive neurorehabilitation according to clinical guidelines.
Topics: Adult; Humans; Activities of Daily Living; Perceptual Disorders; Stroke; Stroke Rehabilitation; Vision Disorders; Randomized Controlled Trials as Topic
PubMed: 36326118
DOI: 10.1002/14651858.CD007039.pub3 -
The Cochrane Database of Systematic... Mar 2023Persistent postural-perceptual dizziness (PPPD) is a chronic balance disorder, which is characterised by subjective unsteadiness or dizziness that is worse on standing... (Review)
Review
BACKGROUND
Persistent postural-perceptual dizziness (PPPD) is a chronic balance disorder, which is characterised by subjective unsteadiness or dizziness that is worse on standing and with visual stimulation. The condition was only recently defined and therefore the prevalence is currently unknown. However, it is likely to include a considerable number of people with chronic balance problems. The symptoms can be debilitating and have a profound impact on quality of life. At present, little is known about the optimal way to treat this condition. A variety of medications may be used, as well as other treatments, such as vestibular rehabilitation. OBJECTIVES: To evaluate the benefits and harms of pharmacological interventions for persistent postural-perceptual dizziness (PPPD). SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 21 November 2022.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) and quasi-RCTs in adults with PPPD, which compared selective serotonin reuptake inhibitors (SSRIs) or serotonin and norepinephrine reuptake inhibitors (SNRIs) with either placebo or no treatment. We excluded studies that did not use the Bárány Society criteria to diagnose PPPD and studies that followed up participants for less than three months. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were: 1) improvement in vestibular symptoms (assessed as a dichotomous outcome - improved or not improved), 2) change in vestibular symptoms (assessed as a continuous outcome, with a score on a numerical scale) and 3) serious adverse events. Our secondary outcomes were: 4) disease-specific health-related quality of life, 5) generic health-related quality of life and 6) other adverse effects. We considered outcomes reported at three time points: 3 to < 6 months, 6 to ≤ 12 months and > 12 months. We planned to use GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: We identified no studies that met our inclusion criteria.
AUTHORS' CONCLUSIONS
At present, there is no evidence from placebo-controlled randomised trials regarding pharmacological treatments - specifically SSRIs and SNRIs - for PPPD. Consequently, there is great uncertainty over the use of these treatments for this condition. Further work is needed to establish whether any treatments are effective at improving the symptoms of PPPD, and whether their use is associated with any adverse effects.
Topics: Adult; Humans; Selective Serotonin Reuptake Inhibitors; Dizziness; Serotonin and Noradrenaline Reuptake Inhibitors; Chronic Disease
PubMed: 36906836
DOI: 10.1002/14651858.CD015188.pub2 -
Annals of Physical and Rehabilitation... Sep 2016Phantom limb pain (PLP) is a major problem after limb amputation. Mirror therapy (MT) is a non-pharmacological treatment using representations of movement, the efficacy... (Review)
Review
BACKGROUND AND OBJECTIVE
Phantom limb pain (PLP) is a major problem after limb amputation. Mirror therapy (MT) is a non-pharmacological treatment using representations of movement, the efficacy of which in reducing PLP remains to be clarified. Here, we present the first systematic review on MT efficacy in PLP and phantom limb movement (PLM) in amputees (lower or upper limb).
METHODS
A search on Medline, Cochrane Database and Embase, crossing the keywords "Phantom Limb" and "Mirror Therapy" found studies which were read and analyzed according the PRISMA statement.
RESULTS
Twenty studies were selected, 12 on the subject of MT and PLP, 3 on MT and PLM, 5 on MT and both (PLP and PLM). Among these 20 studies, 5 were randomized controlled trials (163 patients), 6 prospective studies (55 patients), 9 case studies (40 patients) and methodologies were heterogeneous. Seventeen of the 18 studies reported the efficacy of MT on PLP, but with low levels of evidence. One randomized controlled trial did not show any significant effect of MT. As to the effect of MT on PLM, the 8 studies concerned reported effectiveness of MT: 4 with a low level of evidence and 4 with a high level of evidence. An alternative to visual illusion seems to be tactile or auditory stimulation.
CONCLUSION
We cannot recommend MT as a first intention treatment in PLP. The level of evidence is insufficient. Further research is needed to assess the effect of MT on pain, prosthesis use, and body representation, and to standardize protocols.
Topics: Adult; Amputees; Female; Humans; Imagery, Psychotherapy; Male; Middle Aged; Pain Management; Phantom Limb; Physical Therapy Modalities; Psychomotor Performance
PubMed: 27256539
DOI: 10.1016/j.rehab.2016.04.001 -
The Cochrane Database of Systematic... Mar 2023Persistent postural-perceptual dizziness (PPPD) is a chronic balance disorder, which is characterised by subjective unsteadiness or dizziness that is worse on standing... (Review)
Review
BACKGROUND
Persistent postural-perceptual dizziness (PPPD) is a chronic balance disorder, which is characterised by subjective unsteadiness or dizziness that is worse on standing and with visual stimulation. The condition was only recently defined and therefore the prevalence is currently unknown. However, it is likely to include a considerable number of people with chronic balance problems. The symptoms can be debilitating and have a profound impact on quality of life. At present, little is known about the optimal way to treat this condition. A variety of medications may be used, as well as other treatments, such as vestibular rehabilitation. OBJECTIVES: To assess the benefits and harms of non-pharmacological interventions for persistent postural-perceptual dizziness (PPPD). SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 21 November 2022.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) and quasi-RCTs in adults with PPPD, which compared any non-pharmacological intervention with either placebo or no treatment. We excluded studies that did not use the Bárány Society criteria to diagnose PPPD, and studies that followed up participants for less than three months. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were: 1) improvement in vestibular symptoms (assessed as a dichotomous outcome - improved or not improved), 2) change in vestibular symptoms (assessed as a continuous outcome, with a score on a numerical scale) and 3) serious adverse events. Our secondary outcomes were: 4) disease-specific health-related quality of life, 5) generic health-related quality of life and 6) other adverse effects. We considered outcomes reported at three time points: 3 to < 6 months, 6 to ≤ 12 months and > 12 months. We planned to use GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: Few randomised controlled trials have been conducted to assess the efficacy of different treatments for PPPD compared to no treatment (or placebo). Of the few studies we identified, only one followed up participants for at least three months, therefore most were not eligible for inclusion in this review. We identified one study from South Korea that compared the use of transcranial direct current stimulation to a sham procedure in 24 people with PPPD. This is a technique that involves electrical stimulation of the brain with a weak current, through electrodes that are placed onto the scalp. This study provided some information on the occurrence of adverse effects, and also on disease-specific quality of life at three months of follow-up. The other outcomes of interest in this review were not assessed. As this is a single, small study we cannot draw any meaningful conclusions from the numeric results. AUTHORS' CONCLUSIONS: Further work is necessary to determine whether any non-pharmacological interventions may be effective for the treatment of PPPD and to assess whether they are associated with any potential harms. As this is a chronic disease, future trials should follow up participants for a sufficient period of time to assess whether there is a persisting impact on the severity of the disease, rather than only observing short-term effects.
Topics: Adult; Humans; Dizziness; Chronic Disease; Republic of Korea
PubMed: 36912784
DOI: 10.1002/14651858.CD015333.pub2 -
European Journal of Pain (London,... Jan 2023Phantom limb pain (PLP) concerns >50% of amputees and has a negative impact on their rehabilitation, mental health and quality of life. Mirror therapy (MT) is a... (Review)
Review
Effect of mirror therapy in the treatment of phantom limb pain in amputees: A systematic review of randomized placebo-controlled trials does not find any evidence of efficacy.
BACKGROUND AND OBJECTIVE
Phantom limb pain (PLP) concerns >50% of amputees and has a negative impact on their rehabilitation, mental health and quality of life. Mirror therapy (MT) is a promising strategy, but its effectiveness remains controversial. We performed a systematic review to: (i) evaluate the effectiveness of MT versus placebo in reducing PLP, and (ii) determine MT effect on disability and quality of life.
DATABASES AND DATA TREATMENT
We selected randomized-controlled trials in five databases (Medline, Cochrane Library, CINAHL, PEDro and Embase) that included patients with unilateral lower or upper limb amputation and PLP and that compared the effects on PLP of MT versus a placebo technique. The primary outcome was PLP intensity changes and the secondary outcomes were PLP duration, frequency, patients' disability and quality of life.
RESULTS
Among the five studies included, only one reported a significant difference between the MT group and control group, with a positive MT effect at week 4. Only one study assessed MT effect on disability and found a significant improvement in the MT group at week 10 and month 6.
CONCLUSIONS
Our systematic review did not allow concluding that MT reduces PLP and disability in amputees. This lack of strong evidence is probably due to (i) the low methodological quality of the included studies, and (ii) the lack of statistical power. Future trials should include a higher number of patients, increase the number and frequency of MT sessions, have a long-term follow-up and improve the methodological quality.
SIGNIFICANCE
Recent meta-analyses concluded that MT is effective for reducing phantom limb pain. Conversely, the present systematic review that included only studies with the best level of evidence did not find any evidence about its effectiveness for this condition. We identified many ways to improve future randomized-controlled trials on this topic: increasing the number of participants, reducing the intra-group heterogeneity, using a suitable placebo and intensifying the MT sessions and frequency.
Topics: Humans; Phantom Limb; Quality of Life; Mirror Movement Therapy; Amputees; Pain Management; Randomized Controlled Trials as Topic
PubMed: 36094758
DOI: 10.1002/ejp.2035 -
Annals of Physical and Rehabilitation... Sep 2021Spatial neglect (SN) impedes stroke rehabilitation progress, slows functional recovery, and increases caregiver stress and burden. The estimation of SN prevalence varies... (Review)
Review
OBJECTIVE
Spatial neglect (SN) impedes stroke rehabilitation progress, slows functional recovery, and increases caregiver stress and burden. The estimation of SN prevalence varies widely across studies.
BACKGROUND
We aimed to establish the prevalence of SN based on the injured cerebral hemisphere, recovery stage post-stroke, and diagnostic methodology.
MATERIALS AND METHODS
All journal articles published up to February 27, 2019 from CINAHL, PsycINFO, PubMed and Web of Science were searched. We selected original research articles that described observational studies, included both individuals with left brain damage (LBD) and those with right brain damage (RBD) post-stroke, and reported specific diagnostic methods for SN. All authors reached consensus for the final selection of 41 articles. Time post-stroke, patient selection criteria, study setting, SN diagnostic methods were extracted.
RESULTS
A total of 6324 participants were included: 3411 (54%) with RBD and 2913 (46%) with LBD. Without considering time post-stroke or diagnostic methods, the occurrence rate of SN was 29% (38% after RBD and 18% after LBD). Using ecological assessments resulted in higher prevalence than using tests not directly related to daily life activities (53% vs. 24%). Using methods based on a single-cutoff criterion led to lower occurrence of SN than using multi-test methods (27% vs. 33%). The prevalence decreased from the acute to chronic stage post-stroke.
CONCLUSIONS
The estimated prevalence of SN after unilateral stroke is 30%. SN is more common after RBD than after LBD, but SN after LBD is still quite common. Using ecological assessments and multi-test methods to detect SN is preferred to using a single-cutoff criterion of a test that is not directly related to daily function. The decrease in SN prevalence over time is evident, but the exact prevalence in later stages cannot be estimated. More research is needed to better understand chronic SN.
Topics: Humans; Perceptual Disorders; Prevalence; Recovery of Function; Stroke; Stroke Rehabilitation
PubMed: 33246185
DOI: 10.1016/j.rehab.2020.10.010 -
Schizophrenia Bulletin Jan 2017Hallucinations constitute one of the 5 symptom domains of psychotic disorders in DSM-5, suggesting diagnostic significance for that group of disorders. Although specific... (Review)
Review
Hallucinations constitute one of the 5 symptom domains of psychotic disorders in DSM-5, suggesting diagnostic significance for that group of disorders. Although specific featural properties of hallucinations (negative voices, talking in the third person, and location in external space) are no longer highlighted in DSM, there is likely a residual assumption that hallucinations in schizophrenia can be identified based on these candidate features. We investigated whether certain featural properties of hallucinations are specifically indicative of schizophrenia by conducting a systematic review of studies showing direct comparisons of the featural and clinical characteristics of (auditory and visual) hallucinations among 2 or more population groups (one of which included schizophrenia). A total of 43 articles were reviewed, which included hallucinations in 4 major groups (nonclinical groups, drug- and alcohol-related conditions, medical and neurological conditions, and psychiatric disorders). The results showed that no single hallucination feature or characteristic uniquely indicated a diagnosis of schizophrenia, with the sole exception of an age of onset in late adolescence. Among the 21 features of hallucinations in schizophrenia considered here, 95% were shared with other psychiatric disorders, 85% with medical/neurological conditions, 66% with drugs and alcohol conditions, and 52% with the nonclinical groups. Additional differences rendered the nonclinical groups somewhat distinctive from clinical disorders. Overall, when considering hallucinations, it is inadvisable to give weight to the presence of any featural properties alone in making a schizophrenia diagnosis. It is more important to focus instead on the co-occurrence of other symptoms and the value of hallucinations as an indicator of vulnerability.
Topics: Hallucinations; Humans; Schizophrenia
PubMed: 27872259
DOI: 10.1093/schbul/sbw132 -
The Cochrane Database of Systematic... Oct 2016This is an updated version of the original Cochrane review published in Issue 12, 2011. Phantom limb pain (PLP) is pain that arises in the missing limb after amputation... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an updated version of the original Cochrane review published in Issue 12, 2011. Phantom limb pain (PLP) is pain that arises in the missing limb after amputation and can be severe, intractable, and disabling. Various medications have been studied in the treatment of phantom pain. There is currently uncertainty in the optimal pharmacologic management of PLP.
OBJECTIVES
This review aimed to summarise the evidence of effectiveness of pharmacologic interventions in treating PLP.
SEARCH METHODS
For this update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL, the Cochrane Library), MEDLINE, and Embase for relevant studies. We ran the searches for the original review in September 2011 and subsequent searches for this update up to April 2016. We sought additional studies from clinical trials databases and reference lists of retrieved papers.
SELECTION CRITERIA
We included randomised and quasi-randomised trials studying the effectiveness of pharmacologic interventions compared with placebo, another active treatment, or no treatment, in established PLP. We considered the following outcomes: change in pain intensity, function, sleep, depression or mood, quality of life, adverse events, treatment satisfaction, and withdrawals from the study.
DATA COLLECTION AND ANALYSIS
We independently assessed issues of study quality and extracted efficacy and adverse event data. Due to the wide variability in the studies, we did not perform a meta-analysis for all the interventions and outcomes, but attempted to pool the results of some studies where possible. We prepared a qualitative description and narrative summary of results. We assessed clinical heterogeneity by making qualitative comparisons of the populations, interventions, outcomes/outcome measures, and methods.
MAIN RESULTS
We added only one new study with 14 participants to this updated review. We included a 14 studies (10 with low risk of bias and 4 with unclear risk of bias overall) with a total of 269 participants. We added another drug class, botulinum neurotoxins (BoNTs), in particular botulinum toxin A (BoNT/A), to the group of medications reviewed previously. Our primary outcome was change in pain intensity. Most studies did not report our secondary outcomes of sleep, depression or mood, quality of life, treatment satisfaction, or withdrawals from the study.BoNT/A did not improve phantom limb pain intensity during the six months of follow-up compared with lidocaine/methylprednisolone.Compared with placebo, morphine (oral and intravenous) was effective in decreasing pain intensity in the short term with reported adverse events being constipation, sedation, tiredness, dizziness, sweating, voiding difficulty, vertigo, itching, and respiratory problems.The N-methyl D-aspartate (NMDA) receptor antagonists ketamine (versus placebo; versus calcitonin) and dextromethorphan (versus placebo), but not memantine, had analgesic effects. The adverse events of ketamine were more serious than placebo and calcitonin and included loss of consciousness, sedation, hallucinations, hearing and position impairment, and insobriety.The results for gabapentin in terms of pain relief were conflicting, but combining the results favoured treatment group (gabapentin) over control group (placebo) (mean difference -1.16, 95% confidence interval -1.94 to -0.38; 2 studies). However, gabapentin did not improve function, depression score, or sleep quality. Adverse events experienced were somnolence, dizziness, headache, and nausea.Compared with an active control benztropine mesylate, amitriptyline was not effective in PLP, with dry mouth and dizziness as the most frequent adverse events based on one study.The findings for calcitonin (versus placebo; versus ketamine) and local anaesthetics (versus placebo) were variable. Adverse events of calcitonin were headache, vertigo, drowsiness, nausea, vomiting, and hot and cold flushes. Most of the studies were limited by their small sample sizes.
AUTHORS' CONCLUSIONS
Since the last version of this review, we identified another study that added another form of medical therapy, BoNTs, specifically BoNT/A, to the list of pharmacologic interventions being reviewed for clinical efficacy in phantom limb pain. However, the results of this study did not substantially change the main conclusions. The short- and long-term effectiveness of BoNT/A, opioids, NMDA receptor antagonists, anticonvulsants, antidepressants, calcitonins, and local anaesthetics for clinically relevant outcomes including pain, function, mood, sleep, quality of life, treatment satisfaction, and adverse events remain unclear. Based on a small study, BoNT/A (versus lidocaine/methylprednisolone) does not decrease phantom limb pain. Morphine, gabapentin, and ketamine demonstrate favourable short-term analgesic efficacy compared with placebo. Memantine and amitriptyline may not be effective for PLP. However, results must be interpreted with caution, as they were based mostly on a small number of studies with limited sample sizes that varied considerably and also lacked long-term efficacy and safety outcomes. The direction of efficacy of calcitonin, local anaesthetics, and dextromethorphan needs further clarification. Overall, the efficacy evidence for the reviewed medications is thus far inconclusive. Larger and more rigorous randomised controlled trials are needed for us to reach more definitive conclusions about which medications would be useful for clinical practice.
Topics: Analgesics, Opioid; Anesthetics; Anticonvulsants; Antidepressive Agents; Botulinum Toxins, Type A; Calcitonin; Humans; Neurotoxins; Phantom Limb; Randomized Controlled Trials as Topic; Receptors, N-Methyl-D-Aspartate
PubMed: 27737513
DOI: 10.1002/14651858.CD006380.pub3