摘要:

Cutaneous allodynia, pain resulting from application of a non-noxious stimulus to normal skin, is a recently described symptom of migraine, with a potential role in directing optimal treatment for migraine attacks. Manifestations of cutaneous allodynia include discomfort when combing the hair, shaving, and wearing glasses, contact lenses, earrings or tight clothing.The exact mechanism by which a migraine attack is triggered is not known, but it has been theorised that, in some patients, once the attack has begun, central neurons can propagate information about the pain process without the need for further external stimuli. This process is termed central sensitisation. The trigeminal nerves, which innervate intracranial and extracranial tissues, account for head pain and other symptoms in migraine. The first-order neurons in the trigeminal ganglion receive input from the dural blood vessels, which is transmitted to second-order neurons in the trigeminal brain stem nuclear complex and is finally sent to the third-order neurons in the thalamus. Studies in humans and animals have shown that migraine pain progresses along this neural pathway, with throbbing head pain occurring early in the attack (sensitisation of first-order neurons), followed by central sensitisation and cutaneous allodynia within the referred pain area (second-order) and finally extracephalic allodynia (third-order). The data also indicate that once central sensitisation is established in the second- and third-order neurons, migraine treatment designed to prevent the initiation of central sensitisation can lessen the pain to some extent but cannot reverse it. Thus, treatment affecting the initiation of central sensitisation should be administered immediately after the onset of migraine pain to prevent intracranial hypersensitivity and the establishment of allodynia.The serotonin 5-HT1B/1Dagonist anti-migraine agents (the ‘triptans’) block meningeal nociceptor transmission at presynaptic sites in the dorsal horn. Studies have shown that triptan therapy can abort pain prior to the development of central sensitisation, but not after allodynia has been established. Therefore, in the subset of patients who report symptoms of cutaneous allodynia with migraine attacks, early initiation of triptan therapy is currently the best intervention to achieve rapid, complete and sustained pain relief.

ISSN:1172-7047    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

Depersonalisation disorder is characterised by prominent depersonalisation and often derealisation, without clinically notable memory or identity disturbances. The disorder has an approximately 1 : 1 gender ratio with onset at around 16 years of age. The course of the disorder is typically long term and often continuous. Mood, anxiety and personality disorders are often comorbid with depersonalisation disorder but none predict symptom severity.The most common immediate precipitants of the disorder are severe stress, depression and panic, and marijuana and hallucinogen ingestion. Depersonalisation disorder has also been associated with childhood interpersonal trauma, in particular emotional maltreatment.Neurochemical findings have suggested possible involvement of serotonergic, endogenous opioid and glutamatergic NMDA pathways. Brain imaging studies in depersonalisation disorder have revealed widespread alterations in metabolic activity in the sensory association cortex, as well as prefrontal hyperactivation and limbic inhibition in response to aversive stimuli. Depersonalisation disorder has also been associated with autonomic blunting and hypothalamic-pituitary-adrenal axis dysregulation.To date, treatment recommendations and guidelines for depersonalisation disorder have not been established. There are few studies assessing the use of pharmacotherapy in this disorder. Medication options that have been reported include clomipramine, fluoxetine, lamotrigine and opioid antagonists. However, it does not appear that any of these agents have a potent anti-dissociative effect. A variety of psychotherapeutic techniques has been used to treat depersonalisation disorder (including trauma-focused therapy and cognitive-behavioural techniques), although again none of these have established efficacy to date. Overall, novel therapeutic approaches are clearly needed to help individuals experiencing this refractory disorder.

ISSN:1172-7047    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

▴ A controlled-release (CR) formulation of the SSRI paroxetine has been developed. This CR formulation delays the release of paroxetine until the tablet has passed through the stomach; the drug is then released over 4–5 hours.▴ In well designed placebo-controlled trials in patients with major depressive disorder (including a study in the elderly), social anxiety disorder or premenstrual dysphoric disorder (PMDD), paroxetine CR was consistently superior to placebo with regards to primary endpoints (i.e. mean Hamilton Rating Scale for Depression total score [major depressive disorder], Liebowitz social anxiety scale total score and Clinical Global Impressions-Global Improvement score [social anxiety disorder] and Visual Analogue Scale-Mood score [PMDD]). The duration of treatment was 12 weeks or, in PMDD, over three menstrual cycles (intermittent or continuous administration).▴ Paroxetine CR also demonstrated efficacy in three well designed studies in patients with panic disorder with or without agoraphobia.▴ Paroxetine CR was generally well tolerated in clinical trials, with an adverse-event profile typical of SSRIs, although recipients of paroxetine CR experienced significantly less nausea than recipients of immediate-release paroxetine in the first week of treatment.Table. Features and properties of paroxetine controlled release (CR) [Paxil CR™]

ISSN:1172-7047    

出版商:ADIS    

年代:2004

数据来源: ADIS

ISSN:1172-7047    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

▴ Aripiprazole, an oral quinolinone (carbostyril), is a novel atypical antipsychotic that has partial agonist activity at dopamine D2and serotonin 5-HT1Areceptors, and antagonist activity at 5-HT2Areceptors.▴ Aripiprazole had a rapid onset of action (as early as day 4) and was effective in the treatment of patients with bipolar I disorder experiencing an acute manic or mixed episode. Aripiprazole was generally significantly more effective than placebo in improving manic symptoms (as defined by a mean change in Young Mania Rating Scale Total Score) in 3-week placebo-controlled trials, and demonstrated superior effectiveness to haloperidol (response rate 50% vs 28.4% in patients remaining on treatment) in a 12-week comparative trial.▴ The time to relapse of symptoms in stabilised patients with bipolar I disorder who previously experienced a manic episode was significantly longer with aripiprazole than with placebo in a 26-week relapse prevention study.▴ Aripiprazole was generally well tolerated and was not associated with weight gain, serum prolactin elevation or clinically significant QTc interval prolongation.▴ Changes from baseline in extrapyramidal symptom scale scores with aripiprazole were small (<0.5 units), but generally significantly greater than with placebo in one of the 3-week trials. In the 12-week trial, changes from baseline were significantly smaller with aripiprazole than with haloperidol.Table. Features and properties of aripiprazole (Abilify™)

ISSN:1172-7047    

出版商:ADIS    

年代:2004

数据来源: ADIS

ISSN:1172-7047    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

Mitoxantrone (Novantrone®), a synthetic anthracenedione derivative, is an antineoplastic, immunomodulatory agent. Its presumed mechanism of action in patients with multiple sclerosis (MS) is via immunomodulatory mechanisms, although these remain to be fully elucidated.Intravenous mitoxantrone treatment improved neurological disability and delayed progression of MS in patients with worsening relapsing-remitting (RR) [also termed progressive-relapsing (PR) MS] or secondary-progressive (SP) disease. In a pivotal randomised, double-blind, multicentre trial, mitoxantrone 12 mg/m2administered once every 3 months for 2 years provided significant improvements in neurological disability ratings, including Kurtzke Expanded Disability Status Scale (EDSS), Ambulatory Index (AI) and Standardised Neurological Status (SNS) scores, compared with placebo. The drug also significantly reduced the mean number of corticosteroid-treated relapses and prolonged the time to the first treated relapse, with the beneficial effects on disease progression supported by magnetic resonance imaging.Post hocanalyses suggest that the benefits associated with mitoxantrone treatment may be sustained for at least 12 months after cessation of treatment, mean changes from baseline at 36 months in EDSS, AI and SNS scores of 0.10, 0.61 and 0.19, respectively, in the mitoxantrone group versus 0.46, 1.13 and 3.38 with placebo.Concomitant intravenous mitoxantrone 20mg plus intravenous methylprednisolone 1g once every month for 6 months was more effective than intravenous methylprednisolone monotherapy in preventing the development of new gadolinium-enhanced lesions in patients with very active RRMS or SPMS.The drug was generally well tolerated in patients with MS. Adverse events were generally mild to moderate in severity and usually resolved upon discontinuation of treatment or with appropriate pharmacotherapy. At the recommended dosage, mitoxantrone appears to have a low potential to cause cardiotoxicity.In conclusion, intravenous mitoxantrone reduces the relapse rate and slows progression of the disease in patients with worsening RRMS, PRMS or SPMS; thus providing a new option for the management of these patients. The drug was generally well tolerated at the recommended dosage, although potential cardiotoxicity limits the total cumulative dose to 140 mg/m2. Further studies are warranted to determine which patients with worsening RRMS, PRMS or SPMS are most likely to benefit from mitoxantrone treatment and to more fully define the long-term safety and tolerability of mitoxantrone, including the use of concomitant cardioprotectants to extend the therapeutic lifespan of the drug.

ISSN:1172-7047    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

Atomoxetine (Strattera™) is a selective noradrenaline (norepinephrine) reuptake inhibitor and nonstimulant that has shown greater efficacy than placebo in attention-deficit hyperactivity disorder (ADHD) in adults. In two large, well controlled, 10-week trials in adults with ADHD, improvements in ADHD symptoms, as assessed by investigator- and patient-rated scores, were greater with oral atomoxetine (60, 90 or 120 mg/day) than with placebo. Mean reductions in the total ADHD symptom score on the investigator-rated Conners' Adult ADHD Rating Scale (CAARS) in atomoxetine versus placebo recipients were 28.3% versus 18.1% and 30.1% versus 19.6%, respectively. Mean reductions in the scores on the Clinician Global Impression of Severity Scale, patient-rated CAARS and Wender-Reimherr Adult Attention Deficit Disorder Scale were also significantly greater with atomoxetine than with placebo. Continued efficacy was demonstrated in a noncomparative, 34-week extension phase.Atomoxetine was generally well tolerated in clinical trials; withdrawal rates due to adverse events in atomoxetine- versus placebo-treated patients participating in the two major trials were 7.8% versus 4.3% and 9.3% versus 2.4% (p < 0.05 for the latter trial). Adverse events reported significantly more frequently with atomoxetine than placebo included dry mouth, insomnia, nausea, decreased appetite, constipation, dizziness, sweating, dysuria, sexual problems and palpitations. Modest increases in heart rate and blood pressure were well tolerated and gradually decreased on cessation of treatment. Atomoxetine was not associated with QT interval prolongation.Atomoxetine can be administered once or twice daily. Its subjective-effects profile is different to that of methylphenidate and atomoxetine is not associated with abuse or diversion; it is therefore not a controlled substance in the US. This also means repeat prescriptions during long-term treatment can be more conveniently processed.ConclusionAtomoxetine is an effective and generally well tolerated treatment for adults with ADHD. It is a nonstimulant and is the first ADHD treatment to be approved specifically for adult use based on its efficacy in well controlled adult trials. It can be administered as a single daily dose or split into two evenly divided doses. It carries negligible risk of abuse or diversion and is not a controlled substance. Atomoxetine is a valuable new treatment option for adults with ADHD and is particularly useful in patients who are at risk for substance abuse or who do not wish to take a controlled substance.

ISSN:1172-7047    

出版商:ADIS    

年代:2004

数据来源: ADIS

ISSN:1172-7047    

出版商:ADIS    

年代:2004

数据来源: ADIS