Methylphenidate for the treatment of depressive symptoms,including fatigue and apathy,in medically ill older adults and terminally ill adults

Background: Depressive symptoms, fatigue, and apathy are common symptoms among medically ill older adults and patients with advanced disease, and have been associated with morbidity and mortality. Methylphenidate has been used to treat these symptoms because of its rapid effect. Despite the long history of methylphenidate use for the treatment of depressive symptoms, fatigue, and apathy, there is little definitive evidence to support its use.Objective: The aim of this paper was to review the efficacy and tolerability of methylphenidate in the treatment of depressive symptoms, fatigue, and apathy in medically ill older adults and adults receiving palliative care.Methods: English-language articles presenting systematic reviews, clinical trials, or case series describing the use of methylphenidate for the treatment of depressive symptoms, fatigue, or apathy in medically ill older adults or adults receiving palliative care were identified. The key words methylphenidate and either depressive, depression, fatigue, or apathy were used to search the Cochrane Database, MEDLINE, PsycINFO, and International Pharmaceutical Abstracts. Included articles addressed depressive symptoms, fatigue, or apathy in (1) older adults (generally, age ≥65 years), particularly those with comorbid medical illness; (2) adults receiving palliative care; and (3) adults with other chronic illnesses. I excluded articles regarding treatment of depression in healthy young adults; bipolar disorder and attention-deficit/hyperactivity disorder; and narcolepsy, chronic fatigue syndrome, and related disorders.Results: A total of 19 controlled trials of methylphenidate in medically ill older adults or patients in palliative care were identified. Unfortunately, their conflicting results, small sample sizes, and poor methodologic quality limited the ability to draw inferences regarding the efficacy of methylphenidate, although evidence of tolerability was stronger. The available evidence suggests possible effectiveness of methylphenidate for depressive symptoms, fatigue, and apathy in various medically ill populations.Conclusion: In the absence of definitive evidence of effectiveness, trials of low-dose methylphenidate in medically ill adults with depression, fatigue, or apathy, with monitoring for response and adverse effects, are appropriate.     

Reversal of SSRI-associated apathy syndrome by discontinuation of therapy

OBJECTIVE : To report 6 cases of selective serotonin reuptake inhibitor (SSRI)-associated apathy syndrome. CASE SUMMARIES : In all 6 cases, the patient reported loss of motivation while being treated with an SSRI. Loss of motivation was of new onset and temporally associated with the use of the SSRI. A trial of discontinuation of the SSRI was performed in all 6 patients and 2 were started on bupropion while cross-tapering from the SSRI. During the treatment trials, depression and apathy were monitored in all patients. Each case was assessed using the Apathy Evaluation Scale, Clinician version (AES-C), and by evaluating how the patient responded to discontinuation of the SSRI. DISCUSSION : Scores on the AES-C improved significantly in all 6 cases after the SSRI was discontinued. Improvement was also seen in the motivation, novelty, and persistence subdomain scores of the AES-C. A pretreatment AES-C score was available only in the first case. Based on the Naranjo probability scale, there was a probable cause of apathy syndrome with SSRI therapy in the first case and a possible association in the rest of the cases. CONCLUSIONS : In some patients SSRIs may cause an apathy syndrome that can be reversed through discontinuation of the agent. When evaluating patients being treated with an SSRI, clinicians should have a high degree of suspicion and specifically inquire for this iatrogenic form of apathy syndrome.     

Hypothyroidism and depression: a therapeutic challenge

OBJECTIVE: To describe a patient with longstanding depression and hypothyroidism who had marked mood improvement only after triiodothyronine (T3) was added to her thyroxine (T4) replacement therapy. CASE SUMMARY: A 50-year-old white woman had a long history of depression and documented hypothyroidism since 1991. Despite treatment with T4 with dosages up to 0.3 mg/d, she continued to be depressed, have symptoms of hypothyroidism, and have a persistently elevated thyroid-stimulating hormone concentration. Addition of a low dose of T3 to her regimen resulted in significant mood improvement. DISCUSSION: The relationship between hypothyroidism and depression is well known. It is possible that this patient's long history of depression may have been a consequence of inadequately treated hypothyroidism, due either to poor patient compliance or resistance to T4. Nevertheless, her depression responded to addition of a low dose of T3 to her regimen. This case emphasizes the importance of screening depressed patients for hypothyroidism. Her clinical course also suggests that depression related to hypothyroidism may be more responsive to a regimen that includes T3 rather than to replacement with T4 alone. This is consistent with the observation that T3 is superior to T4 as adjuvant therapy in the treatment of unipolar depression. CONCLUSIONS: Depressed patients should be screened for hypothyroidism. In hypothyroid patients, depression may be more responsive to a replacement regimen that includes T3 rather than T4 alone. Therefore, inclusion of T3 in the treatment regimen may be warranted after adequate trial with T4 alone.     

Depression in a Patient With Alzheimer Disease

This is a case study of a 73-year-old woman recently diagnosed with Alzheimer disease living in an assisted living facility who presented to an outpatient behavioral health clinic with her son for evaluation and treatment of depression. This article highlights the presentation of depression (a diagnosis) versus apathy (a symptom of Alzheimer disease) and the need to assess for co-occurring mood disorders that warrant pharmacologic intervention as well as treatment for cognitive decline in Alzheimer disease.     

Apathy: Who Cares? A Concept Analysis

Apathy has been identified as an independent clinical syndrome. As prevalent and problematic as it is in the field of neuropsychiatry, there is no fully accepted definition of apathy. In this study, a concept analysis utilizing Rodgers’ evolutionary approach was performed. CINAHL Plus with Full Text was searched, and altogether 36 publications were identified for the concept analysis. Our study shows that psychometric scales may have resulted in an inappropriate diagnosis of depression instead of apathy. As a whole, the literature showed that apathy was defined in comparison to depression as well as altered motivation, emotionality, activity, interest, and initiative. We discuss the advances in the development of apathy as an evolutionary concept. Consistent with Rodgers’ evolutionary method, these findings are not an endpoint.     

Antidepressant-Related Apathy: Implications for Practice

Depression remains a mental health disorder managed by primary care providers. Although uncomplicated depression is clear and easy to manage with medication and psychotherapy, there are subtle adverse effects of treatment that can go undetected. This report discusses the relationship between serotonin drugs and apathy syndrome, anatomical changes, and the assessment and clinical implication of apathy syndrome. Management of apathy syndrome is also discussed. Apathy syndrome can be a challenge and debilitating at times. Therefore, primary care clinicians should be aware apathy syndrome as an adverse effect to treatment and proper treatment approaches to relieve it. This could potentially improve compliance with depression treatment.     

脑卒中后焦虑抑郁及神经功能恢复与帕罗西汀及丙咪嗪的干预效应

背景:脑卒中后不仅导致躯体残疾,而且伴随心理损害时常发现抑郁、焦虑症状混合并存,无论焦虑症状是原发的还是继发的,在常规治疗原发病的同时均应同时应用药物治疗焦虑,抑郁症状。目的:探讨合并与不合并应用抗抑郁剂及应用不同抗抑郁剂对脑卒中后神经功能及焦虑、抑郁症状的疗效。设计:以患者为观察对象,随机对照、双盲实验。单位:兰州大学第二医院精神科和神经内科。对象:选择1999-07/2002-12兰州大学第二医院神经内科收治的脑卒中伴有焦虑、抑郁性精神障碍患者90例。随机分为帕罗西汀组、丙咪嗪组和对照组,每组30例,年龄41～72岁。方法:在急性期抢救治疗一两周后,意识清楚,生命体征平稳,无理解功能障碍,对照组常规治疗原发病及康复训练,帕罗西汀组在此基础上,同时服用帕罗西汀20mg/d,丙咪嗪组在此基础上,服用丙咪嗪50～150mg/d,共治疗12周,各组患者在治疗2,4,8,12周末进行神经功能缺损程度、生活自理程度、汉密顿抑郁量表(24项)、汉密顿焦虑量表(14项)评分。焦虑、抑郁症状疗效评估:按汉密顿焦虑、抑郁量表评分的减分率判断,减分率:痊愈>75%;50%≤显效<75%;25%≤进步<50%;无效<25%。神经功能疗效标准:基本痊愈:神经功能缺损程度评分减少90%～100%;显著进步:评分减少46%～89%;进步:评分减少18%～45%;无效:评分减少17%以下或病情恶化。主要观察指标:①各组患者治疗前后神经功能恢复情况。②各组患者治疗前后焦虑、抑郁恢复情况。③各组患者抑郁症状疗效及神经功能疗效。神经功能缺损程度、生活自理程度。④不良事件及副反应。结果:帕罗西汀组中途失访1例,对照组失访3例,丙咪嗪组由于副反应中途脱落3例,进入结果分析83例。①各组患者治疗前后神经功能恢复情况:治疗2,4周神经功能缺损程度、生活自理程度评分值变化较大(P<0.01),8,12周渐趋缓慢(P<0.05);治疗后帕罗西汀组神经功能缺损程度、生活自理程度评分与对照组比较差异有显著性意义(P<0.01),丙咪嗪组与对照组及帕罗西汀组与丙咪嗪组比较差异无显著性意义(P>0.05)。②各组患者治疗前后焦虑、抑郁恢复情况:治疗后2,4,8,12周帕罗西汀组与丙咪嗪组汉密顿抑郁量表、汉密顿焦虑量表评分明显低于对照组(P<0.01～0.001)。治疗12周后帕罗西汀组和丙咪嗪组比较差异无显著性意义(P>0.05)。③帕罗西汀与丙咪嗪对焦虑、抑郁症状有效率为86.6%及85.1%,明显优于对照组(46.6%),帕罗西汀、丙咪嗪和对照组神经功能恢复的有效率分别为89.6%,70.3%;56.6%,帕罗西汀组明显高于对照组(P<0.01),丙咪嗪组与对照组比较(P>0.05)。结论:对脑卒中后焦虑、抑郁及神经功能恢复需合并抗抑郁剂干预,帕罗西汀与丙咪嗪抗焦虑、抑郁疗效相同,前者副作用小,依从性好,对神经功能恢复效更佳。     

Epstein-Barr virus-related encephalitis in a young woman: A case report

Although infectious mononucleosis due to Epstein-Barr virus (EBV) is a common disease among young individuals, central nervous system (CNS) complications are rare. In this report, we describe a case of CNS complications caused by EBV in a previously healthy young woman. She presented to our hospital with a 9-day history of headache and sore throat, followed by the development of fever and facial edema 6 days prior to admission. On Day 2 of admission, she was confused (Glasgow Coma Scale score: 10 points) and had fever, muscle weakness in her right arm and leg, stiff neck, and roving eye movement. We detected EBV in a cerebrospinal fluid (CSF) sample using a polymerase chain reaction (PCR) test. The magnetic resonance imaging of her brain revealed dural enhancement and right parietal and temporal lobe lesions. She was treated with acyclovir and high-dose steroid therapy. She responded well to treatment, recovered without neurologic sequelae, and was discharged home on Day 12.Our experience suggests that PCR detection of EBV DNA in CSF may be useful in diagnosing EBV encephalitis and that prognosis may be associated with an area of the brain that is affected and the time from symptom onset to starting treatment.     

脑卒中后情感淡漠与执行功能障碍、抑郁的相关性分析

目的:探讨急性脑卒中患者卒中后情感淡漠的发生,评价卒中后情感淡漠与抑郁、认知功能障碍、执行功能障碍的关系.方法:连续搜集于住院治疗的符合入组标准的急性脑卒中患者,采用淡漠评定量表-临床医生使用版本(AES-C)于起病后第2周对患者进行评估,根据有无伴发情感淡漠,将患者分为两组,比较两组间临床资料、MoCA、MMSE、HAMD、MDRS I/P评分是否存在显著性差异.评价AES-C评分和情感、认知、执行功能量表评分的相关性.结果:共有65例患者入组,其中22例(33.8%)患者存在情感淡漠症状.伴情感淡漠组患者MDRS I/P评分明显低于无伴情感淡漠组(25.2±2.5 vs.31.9±5.0 P<0.01),Pearson相关分析显示AES-C评分与MDRS I/P评分成负相关(r=-0.54,P<0.01),AES-C评分评分与HAMD评分成正相关(r=0.27,P=0.03).结论:卒中后情感淡漠的严重程度与抑郁程度、执行功能障碍程度明显相关.     

Efficacy of theophylline compared to methylphenidate for the treatment of attention-deficit hyperactivity disorder in children and adolescents: a pilot double-blind randomized trial

Attention-deficit hyperactivity disorder (ADHD) is a common disorder of childhood that affects 3-6% of school children. Conventional stimulant medications are recognized as useful symptomatic treatments by both specialists and parents. Nevertheless, approximately 30% of ADHD children treated with them do not respond adequately or cannot tolerate the associated adverse effects. Such difficulties highlight the need for alternative, safe and effective medications in the treatment of this disorder. Theophylline is a psychomotor stimulant most widely used as a broncodilator. Purinergic modulation may be therapeutically beneficial in the treatment of psychiatric disorders. We hypothesized that theophylline would be beneficial for the treatment of ADHD and report results of a trial of theophylline compared with methylphenidate for the treatment of ADHD. A total of 32 children with ADHD as defined by DSM IV were randomized to theophylline and methylphenidate dosed on an age and weight-adjusted basis at 4 mg/kg/day (under 12 years) and 3 mg/kg/day theophylline (over 12 years) (group 1) and 1 mg/kg/day methylphenidate (group 2) for a 6-week double-blind and randomized clinical trial. The principal measure of the outcome was the Teacher and Parent ADHD Rating Scale. Patients were assessed by a child psychiatrist, at baseline and at 14, 28 and 42 days after start of the medication. No significant differences were observed between theophylline and methylphenidate on the Parent and Teacher Rating Scale scores over the trial (t = 0.49, d.f. = 24 P = 0.62 and t = 0.19, d.f. = 24 P = 0.54 respectively). Although the number of dropouts in the methylphenidate group was higher than the theophylline group, there was no significant difference between the two protocols in terms of the dropouts. In addition, headaches were observed more often in the methylphenidate group. The results suggest that theophylline may be a useful for the treatment of ADHD. In addition, a tolerable side-effect profile is one of the advantages of theophylline in the treatment of ADHD. Nevertheless, our study is small and our results would need to be confirmed in a larger study.     

Quetiapine therapy for posttraumatic stress disorder

OBJECTIVE: To report a case of improvement in posttraumatic stress disorder (PTSD) after adjunctive therapy with quetiapine. CASE SUMMARY: A 49-year-old white man witnessed a traumatic event and experienced severe PTSD. He was started on paroxetine, with increases in dosage and no significant improvement. Quetiapine was added to his regimen, with increased doses resulting in improvement of PTSD symptoms, both clinically and as measured on the Hamilton-D rating scale for depression and the clinician-administered PTSD screen. DISCUSSION: This is the first case published in the English language literature describing improvement in PTSD symptoms after treatment with quetiapine. There are several treatment options for PTSD, but some severe cases may require treatment with antipsychotic medications. Because of the lower risks of serious adverse effects, the newer atypical antipsychotics are much safer than the older antipsychotics. Although use of risperidone and olanzapine in the successful treatment of PTSD has been reported in the literature, there are no reports of quetiapine use in this clinical condition. CONCLUSIONS: Quetiapine appeared to improve clinical signs and symptoms of PTSD in this patient. It may be a treatment option in other severe cases of PTSD.     

Use of a depression screening tool and a fluoxetine-based algorithm to improve the recognition and treatment of depression in cancer patients. A demonstration project

Helping oncologists to identify and treat depression is an important step in improving the overall care of people with cancer. In previous work performed in our community-based, ambulatory oncology outreach network, we validated a depression screening tool, put into place depression screening programs, and taught oncologists how to follow up on screening with brief, reliable clinical interviews. Subsequently, we provided these oncologists with a fluoxetine-based antidepressant algorithm to follow for the treatment of their depressed patients. In this article, we report on the initial experience identifying and treating 35 ambulatory oncology patients who were screened with the Zung Self-rating Depression Scale (ZSDS). Structured follow-up interviews by their oncologist determined whether the patients qualified for a diagnosis of a major depressive episode. These patients then received 1 of 4 treatments based on the algorithm (no treatment, fluoxetine alone, fluoxetine plus bedtime doxepin, or fluoxetine plus methylphenidate). Patients were matched by their oncologist to a prototype patient for each treatment arm based on their symptomatic presentation (i.e., patients requiring a side effect minimization approach were to be placed on fluoxetine alone; patients who had significant insomnia, weight loss, or neuropathic pain were placed on the fluoxetine plus doxepin regimen; those with prominent fatigue were to receive fluoxetine plus methylphenidate). Patients were followed weekly for one month, and then every two weeks for two more months, with telephone assessments of their depression, associated symptoms and overall quality of life. Results suggested that oncologists most often chose the simplest regimen (fluoxetine alone) but that patients uniformly benefited in terms of improved mood and overall quality of life throughout the 12 weeks of follow-up. Our initial experience suggests that oncologists can be empowered to recognize and treat depression in their patients with a screen-and-intervene approach. Such an approach may benefit patients, and, if kept simple, can be incorporated into day-to-day care of people with cancer.     

Painful hallucinations and somatic delusions in a patient with the possible diagnosis of neuroborreliosis

Neuroborreliosis has become the most frequently recognized tick-borne infection of the nervous system in Europe and the United States. In addition to dermatological, cardiac, articular, and neurologic manifestations, psychiatric disorders such as depression, panic attacks, and schizophrenia-like psychosis can also arise. We report on a 61-year-old woman who developed a severe pain syndrome following several tick bites. She was diagnosed with neuroborreliosis; she received various courses of antibiotics over several years, but without any clinical improvement in her condition. Her eventual admission to a psychiatric ward due to mental symptoms and neuroleptic treatment led to a dramatic improvement of her pain symptoms. However, increasing delusions disclosed a psychotic episode, which ceased over time. We discuss therapeutic difficulties and psychiatric complications in the absence of a clear-cut diagnosis of neuroborreliosis. Although this patient might have suffered from late-onset schizophrenia with painful hallucinations right from the start of her disease, the case highlights psychiatric complications that might be associated with neuroborreliosis.     

Three months in the symptom life of a teenage girl undergoing treatment for cancer

The purpose of this case study was to examine the daily symptom experience of a teenage girl, Abby, undergoing treatment for cancer. Quantitative and qualitative data collection and analysis techniques were used to ascertain patterns in daily experiences of pain, nausea, vomiting, retching, stress, sleep alterations, and anxiety. A time-series analysis focused on change and variability in patterns of symptom data. A key finding was that the predictability evident in Abby's symptom patterns were in direct contrast to her perception that there was no predictability or pattern to her symptoms. Her perceived lack of control over her symptoms generated worry, anxiety, and depression and led Abby to question whether she could continue with the treatment. Abby represented a case of "fighting the treatment," as opposed to "fighting the cancer," and it is the difference between these responses that may explain children's overall ability to tolerate intensive chemotherapy.     

Levofloxacin-induced bilateral Achilles tendonitis.

OBJECTIVE: To report a case of possible levofloxacin-induced bilateral Achilles tendonitis. CASE SUMMARY: An 83-year-old white woman presented to her physician with five days of hemoptysis. She was diagnosed with right lower-lobe pneumonia based on chest X-ray, and levofloxacin 500 mg/d po for 10 days was prescribed. Three days into treatment she began having a variety of adverse effects, including severe nausea, constipation, stomach cramps, and dizziness. Signs of tendonitis began three days after treatment and peaked four days after completion of therapy. Two weeks later, she was treated by her podiatrist with an ankle immobilizer and rest. At her three-week follow-up, she had marked improvement in her pain and bruising; however, her symptoms had not completely resolved. DISCUSSION: Tendonitis and tendon rupture are rare adverse effects of fluoroquinolone antibiotics; there are no reports in the literature of levofloxacin-induced tendonitis. As newer fluoroquinolones become available, the postmarketing studies will become increasingly important to capture the data on rare but serious adverse effects not discovered in the premarketing trials. CONCLUSIONS: To our knowledge, this is the first reported case of tendonitis caused by levofloxacin reported in the literature. Reports have been made, however, to the manufacturer via postmarketing surveillance. As more people are treated with newer fluoroquinolones, the clinical incidence of tendon rupture with these agents may become clearer.     

Probable levetiracetam-associated depression in the elderly: Two case reports

Background: Compared with traditional antiepileptic drugs, levetiracetam has a unique mechanism of action and unique properties, including predominant renal excretion and lack of drug-drug interactions. In the elderly, depression associated with levetiracetam has not been reported.Case summaries: A 73-year-old black man (height, 172.7 cm; weight, 92.7 kg; body mass index [BMI], 31 kg/m²) with stage 4 kidney disease was taking levetiracetam 500 mg BID for partial complex seizures. After 5 months of taking medication, new-onset depression, evidenced by depressed mood, weight loss, fatigue, and appearing withdrawn, was noted in this patient. Levetiracetam was discontinued by order of the patient's primary care physician. At a follow-up appointment 4 weeks later, the depressive symptoms had nearly resolved. The patient's Naranjo Adverse Drug Reaction Probability Scale score was 6, indicating levetiracetam to be a probable cause of depression in this patient. In a second case, a 92-year-old white woman (height, 154.9 cm; weight, 54.5 kg; BMI, 22.7 kg/m²) with existing chronic kidney disease and new-onset partial seizure, likely due to a meningioma, was initiated on levetiracetam 500 mg once daily. Depressive symptoms (eg, anhedonia, hypersomnolence, decreased appetite) were noted within 5 weeks. Cessation led to improvement in mood and cognition within 8 days. Based on this patient's Naranjo Adverse Drug Reaction Probability Scale score of 6, levetiracetam was a probable cause of depression in this patient.Conclusions: Levetiracetam was a probable cause of depression in these 2 elderly patients. Cautious use and additional monitoring may be necessary when prescribing levetiracetam to elderly patients, especially when prescribing to those with a history of renal impairment.     

Effects of methylphenidate on fatigue and depression: a randomized, double-blind, placebo-controlled trial

ContextFatigue is highly prevalent in populations with advanced illness and is often associated with depressed mood. The role of psychostimulant therapy in the treatment of these conditions remains ill defined.ObjectivesTo evaluate the response of fatigue and depression in patients with advanced illness to titrated doses of methylphenidate (MP) as compared with placebo.MethodsIn a randomized, double-blind, placebo-controlled trial, 30 hospice patients, both inpatients and outpatients, who had fatigue scores of at least four on a scale of zero to 10 (0 = no fatigue and 10 = worst fatigue), were randomly assigned to receive either 5 mg of MP at 8 am and 1 pm or placebo. Doses of MP were titrated every three days according to response and adverse effects. Home care patients were monitored daily by telephone and visited by a research nurse on Study Days 0 (baseline), 3, 7, and 14. Fatigue was assessed using the Piper Fatigue Scale as the primary outcome measure and validated by the Visual Analogue Scale for Fatigue and the Edmonton Symptom Assessment Scale (ESAS) fatigue score. Subjects in inpatient facilities were interviewed or assessed by staff on an identical schedule. Depressive symptoms were assessed by the Beck Depression Inventory-II, Center for Epidemiologic Studies Depression Scale, and the ESAS depression score. Primary statistical analysis was conducted using repeated-measures multivariate analysis of the variance.ResultsBoth MP- and placebo-treated groups had similar measures of fatigue at baseline. Patients taking MP were found to have significantly lower fatigue scores (Piper Fatigue Scale, Visual Analogue Scale for Fatigue, and ESAS) at Day 14 compared with baseline. The improvement in fatigue with MP treatment was dose-dependent; the mean average effective dose was 10 mg on Day 3 and 20 mg on Day 14 (dose range of 10–40 mg). Placebo-treated individuals showed no significant improvement in fatigue. For patients with clinically significant depression on Day 0, treatment with MP was associated with a significant reduction in all test indices for depressed mood. For the placebo group, the changes in measures of depression were less than observed in the treatment group but were inconsistent between assessment tools. No significant toxicities were observed.ConclusionMP reduced symptoms of fatigue and depression when compared with placebo. The effect of MP on fatigue was dose-dependent and sustained over the duration of the study.     

A case of opiate-insensitive pain: malignant treatment of benign pain.

OBJECTIVE: We report the case of a woman with presumed cancer pain treated with escalating doses of opiates despite no evident improvement in her pain and several deleterious side effects. PATIENT: A 62-year-old woman with cervical myelopathy and a diagnosis of a spinal cord tumor was referred to the University of Washington Medical Center complaining of chest tightness, multiple joint pains, nausea, constipation, seizures and a deteriorating memory. At the time of admission she was confined to her bed with a full-time attendant and was receiving 240 milligrams of intravenous morphine per hour for her pain. INTERVENTION: Diagnostic studies failed to find any evidence of neoplasm and revealed only an old hemorrhage within the cervical spinal cord. A program of increasing physical and occupational therapy and decreasing opiate intake was initiated. RESULTS: Within a month the patient's pain complaints decreased, as did the rest of her presenting complaints. Her activities of daily living greatly increased making attendant care no longer necessary. CONCLUSIONS: This case report illustrates some of the hazards of opioid therapy in the management of patients with chronic pain. Our patient's opiate therapy was expensive, gave her undesirable side effects, and did not reduce her pain complaints or improve her function. In the treatment of chronic pain, of noncancerous or cancerous origin, a) systemic opioids may not be effective in reducing pain complaints in every patient, b) treatment efficacy evaluation should always include functional endpoints, and c) nonefficacious treatments should not be continued indefinitely.     

Modafinil for remitted bipolar depression with hypersomnia

OBJECTIVE: To report 2 cases of bipolar disorder with recent depression in remission with prominent residual hypersomnia, responding well to the addition of the psychostimulant modafinil.CASE SUMMARIES: Two patients with bipolar disorder with recent depressive episodes in remission are presented. Despite the absence of prominent depressive symptoms, both patients had significant hypersomnia, with scores ranging from 15 to 20 (maximum 24) on the Epworth Sleepiness Scale. The addition of modafinil to their medication regimen resulted in a decrease in hypersomnia and improvement in their level of functioning.DISCUSSION: This is the first report (MEDLINE search, October 7, 2003) demonstrating the use of modafinil in the treatment of hypersomnia in bipolar disorder while mood symptoms were in remission. Hypersomnia frequently occurs in depressive episodes and can be disabling when severe. The patients had optimal mood stabilization with mood stabilizers and antidepressants, but continued to experience excessive daytime sleepiness. Conventional stimulants were not considered because of the risk of triggering mania. The addition of the selective psychostimulant modafinil resulted in significant improvement in the hypersomnia, with improvement in functioning. No adverse effects or mood changes were noted.CONCLUSIONS: Modafinil may be a well-tolerated and effective alternative to conventional stimulants in the treatment of hypersomnia, especially in bipolar disorder, where there is considerable risk of switch to mania with stimulant medications. Modafinil may be useful even when depressive symptoms are not prominent.