Adherence therapy improves medication adherence and quality of life in people with Parkinson's disease: a randomised controlled trial.

BACKGROUND: Many factors are associated with medication non-adherence in Parkinson's disease (PD), including complex treatment regimens, mood disorders and impaired cognition. However, interventions to improve adherence which acknowledge such factors are lacking. A phase II randomised controlled trial was conducted investigating whether Adherence Therapy (AT) improves medication adherence and quality of life (QoL) compared with routine care (RC) in PD. METHODS: Eligible PD patients and their spouse/carers were randomised to intervention (RC plus AT) or control (RC alone). Primary outcomes were change in adherence (Morisky Medication Adherence Scale) and QoL (Parkinson's Disease Questionnaire-39) from baseline to week-12 follow up. Secondary outcomes were MDS-UPDRS (part I, II, IV), Beliefs about Medication Questionnaire (BMQ), EuroQol (EQ-5D) and the Caregiving Distress Scale. Blinded data were analysed using logistic and linear regression models based on the intention-to-treat principle. RESULTS: Seventy-six patients and 46 spouse/carers completed the study (intervention: n = 38 patients, n = 24 spouse/carers). At week-12 AT significantly improved adherence compared with RC (OR 8.2; 95% CI: 2.8, 24.3). Numbers needed to treat (NNT) were 2.2 (CI: 1.6, 3.9). Compared with RC, AT significantly improved PDQ-39 (-9.0 CI: -12.2, -5.8), BMQ general harm (-1.0 CI: -1.9, -0.2) and MDS-UPDRS part II (-4.8 CI: -8.1, -1.4). No significant interaction was observed between the presence of a spouse/carer and the effect of AT. CONCLUSION: Adherence Therapy improved self-reported adherence and QoL in a PD sample. The small NNT suggests AT may be cost-effective. A larger pragmatic trial to test the efficacy and cost-effectiveness of AT by multiple therapists is required.

Occupational therapy for patients with Parkinson's disease.

BACKGROUND: Despite drug and surgical therapies for Parkinson's disease, patients develop progressive disability. It has both motor and non-motor symptomatology, and their interaction with their environment can be very complex. The role of the occupational therapist is to support the patient and help them maintain their usual level of self-care, work and leisure activities for as long as possible. When it is no longer possible to maintain their usual activities, occupational therapists support individuals in changing and adapting their relationship with their physical and social environment to develop new valued activities and roles. OBJECTIVES: To compare the efficacy and effectiveness of occupational therapy with placebo or no interventions (control group) in patients with Parkinson's disease. SEARCH STRATEGY: Relevant trials were identified by electronic searches of MEDLINE (1966-April 2007), EMBASE (1974-2000), CINAHL (1982-April 2007), Psycinfo (1806-April 2007), Ovid OLDMEDLINE (1950-1965), ISI Web of Knowledge (1981-April 2007), National Library for Health (NLH) (April 2007), Nursing, Midwifery and Allied Health (NMAP) (April 2007), Intute: Medicine (December 2005), Proquest Nursing Journals (PNJ, 1986 - April 2007); rehabilitation databases: AMED (1985-April 2007), MANTIS (1880-2000), REHABDATA (1956-2000), REHADAT (2000), GEROLIT (1979-2000); English language databases of foreign language research and third world publications: Pascal (1984-2000), LILACS (1982- April 2007), MedCarib (17th Century-April 2007), JICST-EPlus (1985-2000), AIM (1993-April 2007), IMEMR (1984-April 2007), grey literature databases: SIGLE (1980-2000), ISI-ISTP (1982-April 2007), DISSABS (1999-2000), Conference Papers Index (CPI, 1982-2000) and Aslib Index to Theses (AIT, 1716- April 2006), The Cochrane Controlled Trials Register (Issue 2, 2007), the CenterWatch Clinical Trials listing service (April 2007), the metaRegister of Controlled Trials (mRCT, April 2007), Current controlled trials (CCT) (April 2007), ClinicalTrials.gov (April 2007), CRISP (1972-April 2007), PEDro (April 2007), NIDRR (April 2007) and NRR (April 2007) and the reference lists of identified studies and other reviews were examined. SELECTION CRITERIA: Only randomised controlled trials (RCT) were included, however those trials that allowed quasi-random methods of allocation were allowed. DATA COLLECTION AND ANALYSIS: Data was abstracted independently by two authors and differences were settled by discussion. MAIN RESULTS: Two trials were identified with 84 patients in total. Although both trials reported a positive effect from occupational therapy, all of the improvements were small. The trials did not have adequate placebo treatments, used small numbers of patients and the method of randomisation and concealment of allocation was not specified in one trial. These methodological problems could potentially lead to bias from a number of sources reducing the strength of the studies further. AUTHORS' CONCLUSIONS: Considering the significant methodological flaws in the studies, the small number of patients examined, and the possibility of publication bias, there is insufficient evidence to support or refute the efficacy of occupational therapy in Parkinson's disease. There is now a consensus as to UK current and best practice in occupational therapy when treating people with Parkinson's disease. We now require large well designed placebo-controlled RCTs to demonstrate occupational therapy's effectiveness in Parkinson's disease. Outcome measures with particular relevance to patients, carers, occupational therapists and physicians should be chosen and the patients monitored for at least six months to determine the duration of benefit. The trials should be reported using CONSORT guidelines.

Systematic review of antidepressant therapies in Parkinson's disease.

Depression is the most common psychiatric disturbance in Parkinson's disease. We conducted a Cochrane systematic review to assess the efficacy and safety of antidepressant therapies in idiopathic Parkinson's disease. Relevant trials were identified from electronic databases, reference lists and queries to antidepressant manufacturers. Three randomised controlled trials examined oral antidepressants in 106 patients with Parkinson's disease. No eligible trials of electroconvulsive or behavioural therapy were found. In the first arm of the crossover trial by Andersen et al. (n=22), nortriptyline treated patients showed a larger improvement than placebo in a unique depression rating scale after 16 weeks although significance levels were not provided. A parallel group trial by Wermuth et al. (n=37) did not show any significant difference between citalopram and placebo in Hamilton score after 52 weeks. Rabey et al. (n=47) performed an open-label trial comparing fluvoxamine with amitriptyline. Similar numbers in each group had a 50% reduction in Hamilton score after 16 months. Major side effects including visual hallucinations and confusion were reported with fluvoxamine and amitriptyline. Insufficient data on the effectiveness and safety of antidepressant therapies in Parkinson's disease are available on which to make recommendations for their use. Large scale randomised controlled trials are urgently required.

Catechol-O-methyltransferase inhibitors versus active comparators for levodopa-induced complications in Parkinson's disease.

BACKGROUND: As Parkinson's disease progresses the control of the symptoms often requires the addition of other drugs to levodopa. The principle aim of COMT inhibitor therapy is to increase the duration of effect of the levodopa dose and thus reduce the time patients spend in the relatively immobile 'off' phase. OBJECTIVES: To compare the efficacy and safety of adjuvant COMT inhibitor therapy versus active comparators in patients with Parkinson's disease, already established on levodopa and suffering from motor complications. SEARCH STRATEGY: Electronic searches of the Cochrane Controlled Trials Register (The Cochrane Library Issue 1, 2003), MEDLINE (1966-2003), EMBASE (1974-2003), were conducted. Grey literature was hand searched and the reference lists of identified studies and reviews examined. The manufacturers of COMT inhibitors were contacted. SELECTION CRITERIA: Randomised controlled trials of adjuvant COMT inhibitor therapy versus an active comparator in patients with a clinical diagnosis of idiopathic Parkinson's disease and long-term complications of levodopa therapy. DATA COLLECTION AND ANALYSIS: Data was abstracted independently by the authors and differences settled by discussion. The outcome measures used included Parkinson's disease rating scales, levodopa dosage, 'off' time measurements and the frequency of withdrawals and adverse events. MAIN RESULTS: Two trials were found that examined the efficacy of a COMT inhibitor against an active comparator (n = 349). Koller 1998 compared the efficacy of tolcapone versus pergolide (n = 203) over 12 weeks and TSG 1999 compared the efficacy of tolcapone versus bromocriptine (n = 146) over 8 weeks. No trials were found that compared entacapone with active comparators. Tolcapone produced similar benefits to bromocriptine in 'off' time reduction, motor impairment and disability ratings over three months of therapy. Tolcapone produced a greater reduction in levodopa dosage than bromocriptine. Tolcapone produced similar benefits to pergolide in levodopa dose reduction, motor impairment and disability ratings, and in generic health-related quality of life scales over the first two months of therapy. Tolcapone produced a greater improvement in the disease-specific quality of life scale PDQ-39 than pergolide. Nausea, constipation and orthostatic complaints were greater with agonist therapy, but otherwise the frequency of adverse events and withdrawals from treatment were similar with the two classes of adjuvant medication. One patient had significantly elevated liver enzymes whilst on tolcapone, but otherwise the frequency of adverse events and withdrawals from treatment were similar. REVIEWERS' CONCLUSIONS: The two trials comparing tolcapone with the dopamine agonists bromocriptine and pergolide were underpowered to detect clinically relevant differences between them. This is based on medium-term evidence. No evidence was found comparing entacapone with active comparators. Further larger and longer-term trials are required to compare tolcapone with entacapone and COMT inhibitor therapy with alternative adjuvant classes of drug in later Parkinson's disease such as dopamine agonists and monoamine oxidase inhibitors.

Catechol-O-methyltransferase inhibitors for levodopa-induced complications in Parkinson's disease.

BACKGROUND: As Parkinson's disease progresses the control of motor symptoms often requires the addition of other drugs to levodopa. The principle aim of COMT inhibitor therapy is to increase the duration of effect of each levodopa dose and thus reduce the time patients spend in the relatively immobile 'off' phase. OBJECTIVES: To compare the efficacy and safety of adjuvant COMT inhibitor therapy versus placebo in patients with Parkinson's disease, already established on levodopa and suffering from motor complications. SEARCH STRATEGY: Electronic searches of the Cochrane Controlled Trials Register, (The Cochrane Library Issue 1, 2003), MEDLINE (1966-2003), EMBASE (1974-2003), were conducted. Grey literature was hand searched and the reference lists of identified studies and reviews examined. The manufacturers of COMT inhibitors were contacted. SELECTION CRITERIA: Randomised controlled trials of adjuvant COMT inhibitor therapy versus a placebo in patients with a clinical diagnosis of idiopathic Parkinson's disease and long-term complications of levodopa therapy. DATA COLLECTION AND ANALYSIS: Data were abstracted independently by the authors and differences settled by discussion. The outcome measures used included Parkinson's disease rating scales, levodopa dosage, 'off' time measurements and the frequency of withdrawals and adverse events. MAIN RESULTS: Fourteen trials fulfilled the inclusion criteria. 2566 patients with Parkinson's disease and motor fluctuations were included in this review. Eight trials examined entacapone versus placebo in a total of 1560 patients. These trials were between two and twelve months in duration. Six trials examined tolcapone versus placebo in a total of 1006 patients. These trials were between six weeks and twelve months in duration. Both tolcapone and entacapone reduced 'off' time, reduced levodopa dose and modestly improved motor impairments and disability. This was at the expense of increased risk of dyskinesias, nausea, vomiting, and diarrhoea. A few participants taking tolcapone were found to have raised liver enzyme levels. REVIEWERS' CONCLUSIONS: In the management of the motor complications seen in Parkinson's disease, tolcapone and entacapone can be used to reduce off time, reduce levodopa dose, and modestly improve motor impairment and disability. This is based on, at best, medium term evidence. However some participants on tolcapone had raised liver enzymes. This combined with three cases of fatal hepatic toxicity found during post-marketing surveillance has raised concerns over the safety of tolcapone.

Amantadine for dyskinesia in Parkinson's disease.

BACKGROUND: Abnormal involuntary movements known as dyskinesias are amongst the most disabling side-effects of levodopa therapy. It is thought that amantadine, an NMDA-receptor antagonist, may reduce dyskinesias in patients with Parkinson's disease without worsening Parkinsonian symptoms. OBJECTIVES: To compare the efficacy and safety of adjuvant amantadine therapy versus placebo in treating dyskinesia in patients with Parkinson's disease, already established on levodopa, and suffering from motor complications. SEARCH STRATEGY: Electronic searches of The Cochrane Controlled Trials Register (The Cochrane Library Issue 3, 2001), MEDLINE (1966-2001), EMBASE (1974-2001), SCISEARCH (1974-2001), BIOSIS (1993-2001), GEROLIT (1979-2001), OLDMEDLINE (1957-1965), LILACS (1982-2001), MedCarib (17th Century - 2001), PASCAL (1973-2001), JICST-EPLUS (1985-2001), RUSSMED (1973-2001), DISSERTATION ABSTRACTS (2000-2001), SIGLE (1980-2001), ISI-ISTP (1990-2001), Aslib Index to Theses (2001), Clinicaltrials.gov (2001), metaRegister of Controlled Trials (2001), NIDRR (2001) and NRR (2001) were conducted. Grey literature was hand searched and the reference lists of identified studies and reviews examined. The manufacturers of amantadine were contacted. SELECTION CRITERIA: Randomised controlled trials comparing amantadine with placebo in the treatment of dyskinesia in patients with a clinical diagnosis of idiopathic Parkinson's disease. DATA COLLECTION AND ANALYSIS: Data was abstracted independently by NC and KD onto standardised forms and disagreements were resolved by discussion. MAIN RESULTS: Three randomised controlled trials were found comparing amantadine with placebo in the treatment of dyskinesia in patients with idiopathic Parkinson's disease. Three trials were excluded on the basis that they had no control group and a further three did not state whether they randomised the treatment that participants received. The included trials were double-blind cross-over studies involving a total of 53 patients. All three studies failed to present data from the first arm, instead presenting results as combined data from both treatment arms and both placebo arms. Two trials had no wash-out interval between the treatment periods. In view of the risk of a carry-over effect into the second arm, the results of these trials were not analysed. The final trial had a one week wash-out interval but only examined 11 participants. One study reported side-effects of amantadine in 8 of the 18 participants, including confusion and worsening of hallucinations. Another reported reversible edema of both feet in one of eleven participants. REVIEWER'S CONCLUSIONS: Due to lack of evidence it is impossible to determine whether amantadine is a safe and effective form of treatment for levodopa-induced dyskinesias in patients with Parkinson's disease.

Beta-blocker therapy for tremor in Parkinson's disease.

BACKGROUND: The tremor of Parkinson's disease can cause considerable disability for the individual concerned. Traditional antiparkinsonian therapies such as levodopa have only a minor effect on tremor. Beta-blockers are used to attenuate other forms of tremor such as Essential Tremor or the tremor associated with anxiety. It is thought that beta-blockers may be of use in controlling the tremor of Parkinson's disease. OBJECTIVES: To compare the efficacy and safety of adjuvant beta-blocker therapy against placebo for the treatment of tremor in patients with Parkinson's disease. SEARCH STRATEGY: Electronic searches of MEDLINE, EMBASE, SCISEARCH, BIOSIS, GEROLIT, OLDMEDLINE, LILACS, MedCarib, PASCAL, JICST-EPLUS, RUSSMED, DISSERTATION ABSTRACTS, SIGLE, ISI-ISTP, Aslib Index to Theses, The Cochrane Controlled Trials Register, Clinicaltrials.gov, metaRegister of Controlled Trials, NIDRR, NRR and CENTRAL were conducted. Grey literature was hand searched and the reference lists of identified studies and reviews examined. The manufacturers of beta-blockers were contacted. SELECTION CRITERIA: Randomised controlled trials of adjuvant beta-blocker therapy versus placebo in patients with a clinical diagnosis of idiopathic Parkinson's disease. DATA COLLECTION AND ANALYSIS: Data was abstracted independently by two of the authors onto standardised forms and disagreements were resolved by discussion. MAIN RESULTS: Four randomised controlled trials were found comparing beta-blocker therapy with placebo in patients with idiopathic Parkinson's disease. These were double-blind cross-over studies involving a total of 72 patients. Three studies did not present data from the first arm, instead presenting results as combined data from both treatment arms and both placebo arms. The risk of a carry-over effect into the second arm meant that these results were not analysed. The fourth study presented data from each arm. This was in the form of a mean total score for tremor for each group. Details of the baseline scores, the numbers of patients in each group and standard deviations were not provided, meaning that the magnitude and significance of any changes due to therapy could not be calculated. One study reported a substantial fall in heart rate in 14 of the 22 patients, with one patient withdrawing after his heart rate dropped to 56 beats per minute (baseline heart rate was not reported). REVIEWER'S CONCLUSIONS: In view of this lack of evidence, it is impossible to determine whether beta-blocker therapy is effective and safe for the treatment of tremor in Parkinson's disease. The high frequency of bradycardia in one trial raises some concerns about the prescription of beta-blockers to normotensive elderly patients but the study was too small for the true degree of risk to be calculated.

Adherence therapy for medication non-compliant patients with hypertension: a randomised controlled trial.

The objective of this study is to establish the efficacy of adherence therapy (AT) compared with treatment as usual (TAU) in reducing blood pressure (BP) in non-compliant hypertensive patients. This study was designed as a parallel-group single-blind randomised controlled trial. The study was carried out at three general hospital outpatient clinics in Jordan. A total of 136 non-compliant hypertensive patients with a mean baseline BP of 164.5 mm Hg (s.d. 10.0) over 102.2 mm Hg (s.d. 7.0) participated in the study. 7 weekly 20-min sessions of AT in addition to TAU. The main outcome of this study is systolic blood pressure (SBP) at 11-weeks follow-up. In all, 68 patients received TAU and 68 AT. Intention-to-treat analysis included all participants randomised. AT lowered SBP by -23.11 mm Hg (95% CI: -25.85, -20.36) and diastolic BP (DBP) by -15.18 mm Hg (95% CI: -17.55, -12.80) at 11 weeks compared with TAU. Adherence (measured by pill counting) was also improved in the AT group by 37% at 11 weeks compared with TAU. No significant adverse events were reported. AT increases adherence to medication for hypertension which then leads to a clinically important reduction in BP.