Adolescence is a vulnerable developmental phase marked by physical, psychological, and social changes that rapidly expose young people to a wide range of new stressors. When differentiating between bipolar disorder and teenage "acting out," a careful history is important. Adolescent bipolar disorder is a psychiatric illness characterized by fluctuating episodes of mood elevation and depression that is frequently neither recognized nor formally diagnosed. Adolescents with bipolar disorder often manifest a more nonepisodic, chronic course with continuous rapid-cycling patterns than do adults. Pharmacologic treatment of adolescent bipolar disorder is difficult and often requires combination therapy to address comorbidities like attention-deficit/hyperactivity disorder and anxiety disorder. Adjuncts to pharmacologic treatment of bipolar disorder can be beneficial. Psychosocial treatments include family education, enhanced parenting techniques, stress management, and the development of effective coping strategies.
OBJECTIVE To develop a set of recommendations for primary care physicians (PCPs) suggesting how best to communicate with patients, caregivers, and other family members regarding the diagnosis and management of Alzheimer's disease (AD). PARTICIPANTS A national roundtable of 6 leading professionals involved in treating or advocating for patients with AD was convened on March 14, 2008. This roundtable included 4 leading academic physicians with diverse backgrounds (a geriatric psychiatrist, a neuropsychiatrist, a neurologist, and a geriatrician) from geographically diverse regions of the United States, who were invited on the basis of their national reputation in the field and experience working with minority populations with dementia; the executive director of a national AD advocacy organization; the executive director of a national advocacy organization for caregivers; and a medical correspondent with expertise in interviewing and small group leadership. EVIDENCE Expert opinion supported by academic literature (search limited to PubMed, English language, 1996-2008, search terms: Alzheimer's disease, primary care, diagnosis, management, caregiver, family, patient-physician relationship). CONSENSUS PROCESS Moderated dialogue aimed at generating consensus opinion; only statements endorsed by all authors were included in the final article. CONCLUSIONS Diagnosis and management of AD by PCPs, utilizing specialist consultation as needed, may contribute to earlier diagnosis and treatment, improved doctor-patient and doctor-caregiver communication, increased attention to caregiver needs, and better clinical and quality-of-life outcomes for patients and caregivers. A set of expert panel recommendations describing practical strategies for achieving these goals was successfully developed.
OBJECTIVE This review assesses the outcomes of integrating primary care medical services into psychiatric care settings. DATA SOURCES PubMed, the Cochrane database, and PsycINFO were searched using the key words integrated care, family medicine, primary care, and internal medicine in combination with psychiatry or psychiatric clinic and ward to identify reports published between 1980 and December 2009 in English. STUDY SELECTION Four studies evaluating medical care services on a psychiatry ward or in a psychiatry clinic were found. Trials involving psychiatric services in primary care clinics (the medical-psychiatric model) were excluded. DATA EXTRACTION Data describing setting, patient population, intervention, measured outcomes, and discussion points were collected. DATA SYNTHESIS It was learned that several models of integrated care exist, and patients in these integrated groups received more preventive health measures and showed improved scores on the Medical Outcomes Study 36-item Short-Form Health Survey and Behavior and Symptom Identification Scale and reduced rates of specialist referral. CONCLUSIONS These data indicate that placing primary care physicians in psychiatric care settings improves health maintenance, care coordination, and satisfaction with nonpsychiatric medical care. Future studies should further address costs, the training of primary care physicians to deliver care in these settings, and whether this integrated model is more effective in specific populations such as those with schizophrenia.
OBJECTIVE Patients with bipolar disorder are at increased risk of weight gain, which in turn increases the risk for somatic disease and nonadherence to maintenance therapy. Therefore, interventions addressing weight gain are expedient for the management of this disorder. We set out to evaluate the effects of a lifestyle intervention on body mass index (BMI) and cardiovascular and metabolic parameters in patients with bipolar disorder undergoing mood-stabilizing pharmacologic treatment. METHOD Fifty outpatients with bipolar disorder undergoing mood-stabilizing treatment participated in a randomized controlled trial (waiting control group: n = 24 and multimodal lifestyle intervention group: n = 26). Groups consisted of 2 cohorts (cohort 1: March 2005-February 2006; cohort 2: September 2005-August 2006). The intervention lasted 5 months and consisted of 11 group sessions and weekly fitness training. BMI and body weight as well as cardiovascular and metabolic parameters were determined at 3 assessment points: at pretreatment baseline, at 5 months (end of treatment), and at 11 months (6-month follow-up). RESULTS Intention-to-treat analyses showed that the intervention significantly reduced BMI over time (P = .03), with significant and stable mean differences in BMI change between groups of 0.7 kg/m² (95% CI, 0.2-1.3) at 5 months and 0.8 kg/m² (95% CI, 0.1-1.6) at 11 months' follow-up assessment. The lifestyle intervention had no significant effect on cardiovascular and metabolic parameters (all nonsignificant). The BMI reduction was only seen in female patients (P = .003). CONCLUSIONS BMI in patients with bipolar disorder can be reduced with a long-lasting effect by a multimodal lifestyle intervention. However, this effect was only seen in female participants, indicating the need for gender-specific interventions. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00980863.
BACKGROUND Depression is the most common mental disorder, and suicide is its most serious consequence. The primary objective of this study was to evaluate preliminary evidence for the P4 screener as a brief measure to assess potential suicide risk. METHOD The P4 screener was prospectively evaluated in 2 randomized effectiveness trials of primary care (January 2005-June 2008; N = 250) and oncology patients (March 2006-August 2009; N = 309). Potential suicide ideation was assessed at 5 time points in both trials: baseline and 1, 3, 6, and 12 months. The P4 screener asks about the "4 P's": past suicide attempts, suicide plan, probability of completing suicide, and preventive factors. Patients were classified as minimal, lower, and higher risk based upon responses to these 4 items. RESULTS A suicide assessment was triggered 1 or more times by 17.6% (44 of 250) of Stepped Care for Affective Disorders and Musculoskeletal Pain (SCAMP) participants and 16.5% (51 of 309) of Indiana Cancer Pain and Depression (INCPAD) participants at some point in the trial. Of the patients who triggered a suicide assessment, the majority (29 of 44 in SCAMP and 27 of 51 in INCPAD) were classified as minimal risk by the algorithm. Only 1 (0.4%) of the SCAMP participants and 5 (1.6%) of the INCPAD participants were classified as higher risk. Among the latter, the most common factors preventing patients from attempting suicide were the "4 F's": faith, family, future hope, and fear of failing in their attempt. CONCLUSIONS Preliminary findings suggest that the P4 screener may be useful in assessing potential suicide risk in the clinical care of depressed patients as well as in clinical research. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00118430 (SCAMP) and NCT00313573 (INCPAD).
OBJECTIVE To examine the extent of functional impairment associated with generalized anxiety disorder (GAD) in a sample of primary care patients. METHOD Participants (N = 128) were part of the Primary Care Anxiety Project (PCAP), a study conducted in 15 primary care practices in the northeastern United States. Patients were recruited in primary care practice waiting rooms from July 1997 to May 2001. Participants screening positive for anxiety symptoms received a diagnostic interview and an assessment of health-related functioning (Medical Outcomes Study 36-item Short-Form Health Survey [SF-36]). Effect sizes are reported for comparisons of SF-36 scores between patients with a DSM-IV diagnosis of GAD and general population and medical sample norms. RESULTS Relative to general population normative SF-36 scores, primary care patients with GAD evidenced impaired functioning on both the physical and mental component summary scales. Patients with GAD also evidenced greater impairment in psychosocial functioning than that previously reported for samples of patients with major medical illnesses, including type II diabetes, hypertension, recent myocardial infarction, and congestive heart failure. This finding held true even when GAD patients with comorbid medical illnesses and comorbid Axis I mental disorders were excluded from the comparison. CONCLUSIONS Primary care patients with GAD experience substantial impairment that cannot be accounted for by concurrent medical illnesses or comorbid Axis I mental disorders.
To the Editor: Akathisia, which is a distressing adverse reaction, is usually underdiagnosed or misdiagnosed in patients who are treated with selective serotonin reuptake inhibitors (SSRIs). Although cases of fluoxetine-, paroxetine-, sertraline-, fluvoxamine-, and citalopram-induced akathisia are reported in the literature, to our knowledge, escitalopram-induced akathisia has not yet been reported.1 Here, we report a case of escitalopram-induced akathisia that remitted completely after diazepam treatment.
To the Editor: Early adverse events in childhood, including abuse, may be associated with hypothalamic-pituitary-adrenal axis hyperresponsiveness1,2 as well as emotional and psychophysiologic reactivity3–5 (eg, hyperreactivity with the observation of negative images6). Indeed, emotional hyperreactivity is one of the potential findings in bona fide posttraumatic stress disorder (PTSD).7 In this study, we examined emotional responses to positive, negative, and neutral forms of hypothetical media events as a function of history of childhood trauma. Method. Participants were male and female outpatients, aged 18 or older, being seen for outpatient medical care by residents in internal medicine. Exclusion criteria were cognitive (eg, dementia), medical (eg, pain), or intellectual impairment that would preclude the successful completion of a survey booklet. Respondents (N = 70) consisted of 18 men and 52 women, ranging in age from 18 to 84 years (mean = 41.31, SD = 15.46). Most participants were white (91.4%, n = 64), with 3 being African American, 2 hispanic, and 1 Native American. Only 11.4% (n = 8) had not graduated from high school; 54.3% (n = 38) had earned a high school diploma, 15.7% (n = 11) had completed some college coursework but not a degree, 11.4% (n = 8) had earned an undergraduate degree, and 7.1% (n = 5) had earned a graduate degree. During the appointment, patients were invited into the project as time allowed (ie, a sample of convenience). Participants completed a 6-page research booklet that explored demographic information and emotional reactions to 21 author-developed hypothetical media events. Each item was assessed by the respondent as negative or positive. Then, using a 5-point Likert-style scale, respondents were asked to rate the intensity of their emotional reaction to each event from “very minimal” to “very strong.” Finally, with yes/no response options, participants were asked about any childhood history (ie, before age 12) of sexual, physical, or emotional abuse; the witnessing of violence; and/or physical neglect. Each form of abuse was followed by a brief explanation or definition. Results. To create scales for the media items corresponding to positive, negative, and neutral forms of media events, respondents’ ratings were subjected to factor analysis. Based on these results, as well as examination of scale reliabilities with and without potential items, 3 such scales were constructed (ie, positive items, negative items, and neutral items), each comprising 5 items (see Table 1). Table 1. Categorization of Hypothetical Media Items The positive items (1, 3, 5, 6, 14) demonstrated an internal consistency coefficient (α) of .85, and each item was rated as positive by 83%–92% of respondents. The negative items (2, 7, 13, 15, 21) demonstrated an internal consistency coefficient (α) of .94, and each item was rated as negative by 67%–80% of respondents. The neutral items (9, 10, 12, 19, 20) demonstrated an internal consistency coefficient (α) of .84, and each item was rated as positive by 59%–86% of respondents. We next calculated the correlations between the number of different forms of childhood trauma experienced and ratings of the intensity of emotional reactions to positive (r = 0.16, P < .24), negative (r = 0.24, P < .08), and neutral (r = 0.37, P < .01) media events. The mean rating of the neutral items by participants with no childhood trauma was 1.68, whereas it was 2.34 for those with at least one form of childhood trauma. Note that while the absolute differences are relatively small in magnitude from a clinical perspective, they provide some modest sense of subtle between-group differences. These findings support the current literature by indicating that traumatized individuals may display hyperreactive responses to environmental stimuli. However, a novel finding is that participants demonstrated overreactivity only to neutral or possibly ambiguous events. Previous literature indicates a likely overreactivity to negative events, as in PTSD. Perhaps less traumatized individuals show different patterns of reactivity (eg, hyperresponses to ambiguous stimuli), which is potentially relevant for clinicians working in the field of trauma. The limitations of this study include the small sample size, the self-report nature of the data, and the use of a nonstandardized assessment of childhood trauma. However, these are unexpected and novel findings, and they provide some potential direction for the clinician in terms of symptom inquiry and treatment.
To the Editor: The frequency of methamphetamine use has alarmingly increased in Iran, as in many other countries in recent years.1 The most recent survey on drug abuse in Iran, performed a couple of years ago, showed that only a minority of the Iranian substance abusers (3.6%) used methamphetamine.2 However, in the past 2 years and with the local production of methamphetamine, its price has dropped to less than one-fifth its former price. Methamphetamine use has increased several-fold in that time, and current nonofficial estimates suggest that methamphetamine is currently the second or third most widely used illicit substance in Iran, which means its use is in a real epidemic state. Moreover, many of the patients who abstain from opioids, including the patient described in the present case, turn to methamphetamine as an assumed “non-addicting” substitute. As a result, methamphetamine-induced psychosis has substantially increased and an overwhelmingly increasing number of these individuals are admitted every day to psychiatric emergency settings.3
OBJECTIVE To evaluate the long-term safety, tolerability, and efficacy of 2 strategies for switching from donepezil to rivastigmine transdermal patches in patients with mild to moderate Alzheimer's disease. METHOD This was a prospective, 25-week, randomized, open-label, parallel-group study to evaluate an immediate or delayed switch (7-day withdrawal) from donepezil (5 to 10 mg/d) to rivastigmine transdermal patches (4.6 mg/24 h). Participants included male and female patients, aged ≥ 50 years, with a DSM-IV-TR diagnosis of mild to moderate dementia of the Alzheimer's type, defined as a Mini-Mental State Examination score of 10-24, inclusive. Patients were enrolled between February 2007 and February 2008. The study was split into a 5-week core phase and a 20-week extension phase. Safety and efficacy results from the extension phase are presented. RESULTS Both switching strategies were well tolerated. Rates of discontinuation for any reason were similar between the groups. Discontinuations due to adverse events were also similar, and the incidence of gastrointestinal adverse events was low. Apart from Alzheimer's Disease Cooperative Study-Activities of Daily Living Scale scores, at the end of the study, there was no statistically significant change from baseline in cognitive, behavioral, or global outcomes. Over half of the patients preferred rivastigmine transdermal patches to a tablet. CONCLUSIONS This study suggests that the majority of patients receiving donepezil tablets can be safely switched to rivastigmine transdermal patches without significant deterioration in cognition, behavior, and global functioning. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00305903.
To the Editor: Patients affected by Tourette's syndrome (TS) suffer from sudden, involuntary, repetitive muscle movements (motor tics) and vocalizations (vocal tics). TS is also known as Gilles de la Tourette syndrome, named for the neurologist who first described the syndrome in 1885. The nature and complexity of the tics are usually variable over time, with natural waxing and waning in frequency and severity.1 Many patients also develop associated behavioral problems, such as obsessions and compulsions, inattention, hyperactivity, and impulsivity.2 Symptom onset typically occurs during childhood or early adolescence.3 The etiopathogenesis of Gilles de la Tourette syndrome has not been ascertained, but it seems that the frontal-subcortical neural pathways are involved.4 TS is frequently associated with attention-deficit/hyperactivity disorder, obsessive-compulsive disorder, and behavior problems that impair daily life.2 Duloxetine is a monoamine agonist, mainly used to treat depressive patients. For that reason, my colleagues and I investigated its efficacy for a patient suffering from TS. Case report. I describe a 14-year-old girl 6 years after the onset of TS. Disease onset occurred in 2006 with involuntary, repetitive muscle movements and vocalizations. No triggering factors or accompanying symptoms could be identified. Family history was negative for sleep or other neurologic disorders. Comorbidities, especially attention-deficit/hyperactivity disorder, had been excluded by clinical interview and the Conners Rating Scales5; obsessive-compulsive spectrum disorders have been excluded by clinical interview. A routine electroencephalogram revealed no abnormalities and indicated the absence of epileptiform activities. We initiated duloxetine at 40 mg/d and continued treatment for 4 consecutive weeks. Six days after the start of treatment, improvement of both the involuntary muscle movements and the vocalizations was noticed (on the Yale Global Tic Severity Scale,6 the total motor score decreased from 17 to 10 and the total phonic score decreased from 18 to 12). The patient stated that she experienced a significant improvement of the symptoms. This is the first report to my knowledge illustrating the clinical efficacy of duloxetine in TS. If confirmed in controlled trials, this finding suggests efficacy of duloxetine in this disorder.
To the Editor: Gaitonde et al1 first reported a case of a patient with both burning mouth syndrome (BMS) and vulvodynia. Petruzzi et al2 reported 5 serial cases of vulvostomatodynia. They comment that BMS and vulvodynia may share a common cause. The cause of “dynias” is currently unknown. Here, we report a case of a woman with glossovulvodynia and underlying affective disorder. Venlafaxine brought about dramatic improvement in the patient's symptoms. Case report. Ms A, a 48-year-old woman, started to develop a severe burning sensation in the vulva, palate, throat, and tongue in February 2009. She was evaluated by her dermatologist, neurologist, and dentist. A complete laboratory test was undertaken, with vitamins B12 and B6, folic acid, iron, zinc, thyroid hormones, glucose, and autoimmune panel analyzed. Allergologic study findings were within normal limits. There was no evidence of infection, trauma, or dermatitis in the oral cavity or vulva. Temporomandibular joint function was within the normal range, and she had no prosthetic device. Local and systemic diseases were excluded. She was diagnosed with glossovulvodynia. The patient was treated with trazodone, alprazolam, escitalopram, and paroxetine, with no improvement of her symptoms. She was referred to our psychiatric outpatient clinic in June 2009. Ms A said that she had lost interest in activities that she previously found pleasurable. She could not follow a conversation and felt insecurity and pessimism. She said everything was “going bad” and that she did not have enough money to make ends meet. Her family said she was irritable. She was very anxious and exhibited psychomotor restlessness, depressed mood with guilt, and hypochondriac and ruinous delusions. She suffered from global insomnia and hyporexia. She had diminished ability to think or concentrate. Oral and vulvar symptoms were registered using a 10-cm Visual Analog Scale (VAS; 0 = no pain to 10 = extreme pain); her initial VAS score was 9. The patient completed the Beck Depression Inventory (BDI)3; her initial BDI score was 40. She was diagnosed with major depressive disorder, a severe single episode with mood-congruent psychotic features and melancholic symptoms according to DSM-IV-TR classification. We started administration of venlafaxine (the initial dosage was 37.5 mg/d and the dosage was then gradually increased to 225 mg/d) and lorazepam (2.5 mg/d), with excellent progress: after 10 weeks of treatment, dysesthetic sensations disappeared and Ms A's mood improved until total resolution of the disorder (final VAS score = 0, final BDI score = 5). Glossodynia, or BMS, and vulvodynia are among the psychodermatologic disorders. Therefore, strong relationships with psychopathologic disorders exist, basically with affective disorder, as in the case we report.4 Venlafaxine is a serotonin-norepinephrine reuptake inhibitor (SNRI). It has been repeatedly suggested that depression and pain may share a common psychopharmacology. SNRIs have been studied extensively and have demonstrated efficacy for painful symptoms associated with depression, diabetic neuropathy pain, and chronic pain with or without depression. SNRIs produce higher rates of response and remission from major depression than the selective serotonin reuptake inhibitors (SSRIs), and SNRIs are more effective in the treatment of pain than SSRIs.5–7 In the case we report, we think that venlafaxine resolved the dysesthesias due to its antidepressive effect and because of the disappearance of affective disorder. A detailed assessment of the coexisting psychopathologic disorders is necessary to choose the proper treatment of “dynias.” Nevertheless, many studies support the analgesic effect without taking account of antidepressive effect, so it should resolve other “dynias” when the affective component is not so important.5,6
OBJECTIVEThis study sought to examine the prevalence rates of and gender differences among impulse-control disorders in a college sample.METHODDuring the fall semester of 2006, 791 college students from 2 private colleges in the Midwest completed a self-administered, modified version of the Minnesota Impulse Disorders Interview to assess lifetime rates of DSM-IV-TR-diagnosed impulse-control disorders. Participation was voluntary and anonymous.RESULTSThe mean age of the sample was 20.0 +/- 1.25 years, with females comprising 67.9% of the respondents. Of the individuals, 10.4% (n = 82) met criteria for at least 1 lifetime impulse-control disorder. The most common disorders were trichotillomania (3.91%) and compulsive sexual behavior (3.66%). Kleptomania was the least common (0.38%). Males were significantly more likely to screen positive for pathological gambling (P = .003) and compulsive sexual behavior (P = .002). Females were more likely to have compulsive buying (P = .033).CONCLUSIONSImpulse-control disorders appear to be common among college students. The high rates indicate that these disorders may be incipient during late adolescence and early adulthood and should be addressed prior to onset of clinical versions of the impulse-control disorder.
Because many patients with bipolar disorder seek treatment in primary care practices, physicians in these settings need to be able to diagnose bipolar disorder and common psychiatric and medical comorbidities and to initiate and manage treatment. Unfortunately, bipolar disorder is often underrecognized. The most common symptoms in patients with bipolar disorder are depressive, but these patients may also have anxiety, mood swings, sleep problems, irritability, difficulty concentrating, relationship issues, alcohol- or drug-related problems, and infections. Social and family history and screening tools can help clarify diagnosis. The goal of treatment should be recovery, but periodic relapse and medication nonadherence should be expected. Primary care physicians should decide what level of intervention their practices can support. To manage these patients effectively, practices may need to train office staff, set up monitoring and follow-up systems, establish links with referral and community support services, develop therapeutic alliances with patients, and provide psychoeducation for patients and significant others. Receiving comprehensive psychiatric and medical care and support can be life-changing for patients with bipolar disorder and their families.
OBJECTIVEZolpidem, a nonbenzodiazepine hypnotic, is very effective and widely prescribed in clinical practice for the treatment of insomnia and is thought to have few adverse effects. However, zolpidem-induced adverse effects have begun to be reported in the literature, but few systemic descriptions of the adverse effects (especially for psychotic reactions) of zolpidem have been undertaken. In light of the accumulating reports of adverse reactions to zolpidem, we present 2 case reports of zolpidem-induced adverse effects and review the literature on this subject.DATA SOURCESArticles were selected by the authors on the basis of our experience and by a PubMed search using the terms zolpidem or side effects or adverse effects or adverse reactions.STUDY SELECTION AND DATA EXTRACTIONPublications relevant to the objective of this article were obtained (1992-2010), and some adverse neuropsychiatric reactions were summarized.DATA SYNTHESISZolpidem has been associated with the development of adverse neuropsychiatric reactions, such as hallucinations/sensory distortion, amnesia, sleepwalking/somnambulism, and nocturnal eating. The following 4 variables should be considered when prescribing zolpidem: (1) gender: women have been found to have a significantly higher serum zolpidem concentration than men; (2) zolpidem dose: the adverse reactions that develop are dose dependent; (3) protein binding affinity: a high proportion of zolpidem is protein bound; therefore, low serum albumin results in a higher level of free zolpidem leading to adverse psychiatric reactions; and (4) cytochrome P450 (CYP) isoenzyme inhibition: concomitant administration of zolpidem and other drugs may cause interactions that lead to increased concentrations of zolpidem.CONCLUSIONSZolpidem is clinically very effective in treating insomnia. However, while rare, zolpidem-induced unusual complex behavior may develop. Primary care physicians should be alert to the possible unusual complex adverse effects of zolpidem.
Article Abstract Submitted: December 24, 2008; accepted February 22, 2009. Published online: February 11, 2010. Corresponding author: Jeff C. Huffman, MD, Massachusetts General Hospital, 55 Fruit St, Warren 1220C, Boston, MA 02114 (jhuffman@partners.org).
To the Editor: Weight gain is a major problem with second-generation antipsychotics.1 Risperidone is generally considered to be of moderate risk in inducing weight gain when compared to other second-generation antipsychotics. We report the case of a patient diagnosed with schizophrenia, catatonic type, who gained 84 lb (38.1 kg) during 14 months of therapy with long-acting injectable risperidone.
To the Editor: Depression is present in about 20%–40% of dementia patients; 15%–50% of Alzheimer's dementia patients have depression.1,2 Depression is common in the early stages of the disease and remains fairly constant through most stages of Alzheimer's dementia.3 Depression exacerbates the cognitive deficits of the preexisting dementia. In Alzheimer's dementia, mild to moderate depression may also manifest as new onset of agitation, wandering, apathy, insomnia, or change in functional status. Depressive symptoms in dementia should be viewed as a cause of significant and treatable “excess disability.”4 Case report. Ms A, an 80-year-old woman, presented with a 2-year history of cognitive decline and an 8-month history of minor depression. Depression features included low mood with decreased interest in social activities, being less energetic, psychomotor slowing, and being more withdrawn and lonely. Sleep and appetite were good. She met only 3 of the 9 features of the DSM-IV criteria for major depressive disorder. Her Geriatric Depression Scale (GDS)5 score was 11/30. Her Cornell Scale for Depression in Dementia6 score for depression in dementia was 13. Her Mini-Mental State Examination (MMSE)7 score was 22/30, and she met the DSM-IV criteria for Alzheimer's dementia. Computed tomography scan of the brain revealed generalized atrophy. Ms A was started on galantamine 8 mg orally twice a day, which was subsequently increased to 16 mg orally twice a day after 4 weeks. Her minor depression features responded very well with galantamine monotherapy after 2 months. At that time, her MMSE score was 23/30, her GDS score was 4/30, and her Cornell Scale for Depression in Dementia score was 6. Depression is associated with defects of multiple neurotransmitters, including serotonin, dopamine, catecholamine, and acetylcholine. Depression in Alzheimer's dementia is linked to catecholaminergic deficit or degeneration of serotonergic neurons, and this process is also known to occur early in Alzheimer's dementia.8 Galantamine is an acetylcholinesterase inhibitor and an allosteric modulator of nicotinic acetylcholine receptor (nAChR) and is used in the treatment of dementia. Nicotinic acetylcholine receptors exist not only on neuronal cell bodies and dendrites but also on those located on axon terminals and are involved in the modulation of multiple neurotransmitter releases. Neuronal nAChR is a family of ligand-gated ion channels that are widely distributed in the brain and are controlled by acetylcholine and nicotine receptor agonists. In the genetically depressive rats, nicotine showed antidepressant-like effects through the involvement of α4β2 nicotinic acetylcholine receptor subtype. The α4 subunit in combination with the β2 subunit mediates dopaminergic and nonadrenergic release.9 Modulation of nAChR facilitates the release of a number of neurotransmitters, including acetylcholine, dopamine, norepinephrine, serotonin, γ-aminobutyric acid (GABA), and glutamate.10 Striatal nicotinic acetylcholine receptors with high affinity for nicotinic agonists are involved with the release of a number of neurotransmitters, including dopamine.11 Dopamine deficiency is associated with anhedonia, lack of interest, and psychomotor slowing (bradyphrenia), and it may arise as a consequence of cholinergic defects involving nAChR. Studies suggest galantamine in addition to mediating cholinergic neurotransmission also through nicotinic acetylcholine receptors may influence several other neurotransmitter systems, possibly modulating the activity of serotonin, dopamine, glutamate, and GABA in certain nerve tracts.12,13 So, it is possible that galantamine, a cholinesterase inhibitor used in the treatment of dementia, may also have some antidepressant effect. If large studies prove this effect, we may not need to use an antidepressant in addition to a cholinesterase inhibitor in patients who have depression with dementia. This means less medication usage and potentially less adverse effect to these patients.
Article AbstractThe following are excerpts from an address made during the graduation ceremony of the University of Connecticut (UCONN)/St. Francis Family Medicine Program residents on June 28, 2009, at Indian Hills Country Club, Newington, Connecticut. Dr Orientale is an associate professor in family medicine at the UCONN Health Center and has served as program director of the UCONN/St. Francis Family Medicine Residency Program for the past 5 years.Prim Care Companion J Clin Psychiatry 2010;12(3):e1-e2Submitted: September 11, 2009; accepted November 5, 2009. Published online: June 10, 2010 (doi:10.4088/PCC.09m00887whi). Corresponding author: Eugene Orientale Jr, MD, University of Connecticut/St. Francis Family Medicine Residency Program, 99 Woodland St, Hartford, CT 06105 (eorienta@stfranciscare.org).
To the Editor: Akathisia is a common side effect of neuroleptics or dopamine D2 receptor antagonists in the treatment of schizophrenia. Dopamine D2 receptor antagonists are also used as antiemetic agents in cancer patients and can induce akathisia. However, akathisia in palliative care is often unrecognized by general physicians or oncologists.1,2 Akathisia may cause patients severe distress, but a major depressive–like episode secondarily induced by antiemetics in a cancer patient has not been reported. We report a case of a breast cancer patient who suffered from a severe major depressive–like episode induced by akathisia. Case report. In September 2009, Ms A, a 37-year-old woman, was referred to us by a surgeon for investigation of anxiety. She had undergone surgery for left breast cancer at 32 years of age. Since 2007, she has received radiation and chemotherapy for the treatment of metastases to the lungs and parasternal lymph nodes. To relieve pain, oxycodone tablets (5 mg/d) had been prescribed with prochlorperazine (5 mg/d) as an antiemetic agent for 6 months, and 5 weeks previously the dose of oxycodone had been increased to 10 mg/d due to increased breast pain in conjunction with the increased dose of prochlorperazine (10 mg/d). Despite her pain, her activities of daily living were maintained well and she was able to enjoy her life, in activities such as travel with her family. Two weeks before her presentation, she suddenly experienced restlessness of her limbs and anxiety, and she began to walk all day long. Insomnia and loss of appetite appeared. Her restlessness was quite burdensome, and she became severely depressed with suicidal ideation. She was unable to do anything other than walking and moving her limbs. She had no past history of psychiatric disorders, including depression and mania. On our psychiatric examination, all 9 symptoms listed as diagnostic criteria for a major depressive episode in DSM-IV-TR3 were present. Her score on the 17-item Hamilton Depression Rating Scale (HDRS)4 was 36. However, typical symptoms of akathisia such as restlessness, fidgety movement of the legs, and inability to sit or stand still were also observed. Neurologic examination revealed slight Parkinson's syndrome, with disturbance of the gait including lack of arm swing and brachybasia, but without tremor or muscle rigidity. On the basis of the symptoms and their time course, we strongly suspected prochlorperazine-induced akathisia and substance-induced mood disorder (severe depression). We recommended that she discontinue prochlorperazine and gave her supportive psychotherapy without prescribing antidepressants since her severe depression was strongly suspected to have been triggered by neuroleptic-induced akathisia. Following discontinuation of prochlorperazine, her akathisia improved dramatically. One week later, her akathisia was only episodic and of short duration, rather than continuous. Her depression disappeared with recovery from akathisia (HDRS score = 5). Akathisia usually develops as an acute extrapyramidal sign within a few weeks of starting or raising the dose of a neuroleptic medication (DSM-IV-TR).3 Although she had taken prochlorperazine for 6 months, an increase in the dose of prochlorperazine triggered akathisia. Akathisia is commonly observed in the treatment of schizophrenia with neuroleptics, but it is not well known that it can develop during palliative care of patients with antiemetic agents, such as prochlorperazine and metoclopramide, which block central D2 receptors. Prochlorperazine has a very high affinity for D2 receptors comparable to that of haloperidol5 and is likely to induce akathisia and other extrapyramidal side effects. Akathisia induced by D2-blocking antiemetic agents is frequently unrecognized in cancer patients.1,2 Half of 24 cancer patients receiving metoclopramide and prochlorperazine developed akathisia.1 Twenty of 483 patients referred to a department of psychiatry developed akathisia from an antiemetic drug (80% of such patients took prochlorperazine).2 Major depression is also highly prevalent in cancer patients.6 However, most oncologists and general physicians may be unaware that antiemetic-induced akathisia can cause severe depression with suicidality resembling major depressive disorder. Although prochlorperazine is one of the first-line drugs for the treatment of emesis induced by chemotherapy and opioids and is useful in caring for cancer patients, physicians should recognize that it, as well as D2-blocking antiemetic agents other than domperidone, may have pronounced side effects. Long-term use of prochlorperazine should be avoided, or domperidone, a peripherally acting D2 antagonist, should be substituted for it if possible.
