Background: The short-term risk of suicide after medical hospital discharge is four times higher among men compared with women. As previous work has identified female-specific antecedents of suicide-related behavior after medical hospitalization of women with serious mental illness, we examined predictors among a similar population of men with multimorbidity.Methods: Classification and regression tree (CART) models were developed and validated using electronic health records (EHRs) from 1,423,161 medical (non-psychiatric) hospitalizations of men >= 18-years-old with an existing diagnosis of a depressive disorder, bipolar disorder, or chronic psychosis. Hospitalizations occurred between 2009 and 2017. Risk groups were evaluated using an independent testing set. The primary outcome was readmission within one year associated with ICD-9 or -10 code for self-harm or attempt.Results: The 1-year readmission rate for intentional self-harm and suicide attempt was 3.9% (55,337/1,423,161 hospitalizations). The classification model discriminated risk with area under the curve (AUC) 0.73 (Confidence Interval [95%CI] 0.68-0.74), accuracy 0.82 (95%CI 0.71-0.83), sensitivity 82.6% (95%CI 81.2-84), and specificity 83.1% (95%CI 81.7-84.5). Strongest predictors were medical comorbidity, prior self-harm, age, and prior hospitalization. Men with greater medical comorbidity burden and prior self-harm were at highest risk (Odds Ratio [OR] 3.10, 95%CI 3.02-3.18), as were men < 62-years-old with few medical comorbidities (OR 1.11 95% CI 1.08-1.13).Limitations: The study focused on medical hospitalizations for suicide attempt and thus captured only severe attempts resulting in hospitalization. Conclusions: After medical hospitalization, men with serious mental illness experienced a high risk of self-harm (1:25 hospitalizations). Risk was particularly elevated among younger patients without prior medical conditions and older patients with medical comorbidity and prior self-harm.

BACKGROUND:Suicide prevention is a public health priority, but risk factors for suicide after medical hospitalization remain understudied. This problem is critical for women, for whom suicide rates in the United States are disproportionately increasing.OBJECTIVE:To differentiate the risk of suicide attempt and self-harm following general medical hospitalization among women with depression, bipolar disorder, and chronic psychosis.METHODS:We developed a machine learning algorithm that identified risk factors of suicide attempt and self-harm after general hospitalization using electronic health record data from 1628 women in the University of California Los Angeles Integrated Clinical and Research Data Repository. To assess replicability, we applied the algorithm to a larger sample of 140,848 women in the New York City Clinical Data Research Network.RESULTS:The classification tree algorithm identified risk groups in University of California Los Angeles Integrated Clinical and Research Data Repository (area under the curve 0.73, sensitivity 73.4, specificity 84.1, accuracy 0.84), and predictor combinations characterizing key risk groups were replicated in New York City Clinical Data Research Network (area under the curve 0.71, sensitivity 83.3, specificity 82.2, and accuracy 0.84). Predictors included medical comorbidity, history of pregnancy-related mental illness, age, and history of suicide-related behavior. Women with antecedent medical illness and history of pregnancy-related mental illness were at high risk (6.9%-17.2% readmitted for suicide-related behavior), as were women below 55 years old without antecedent medical illness (4.0%-7.5% readmitted).CONCLUSIONS:Prevention of suicide attempt and self-harm among women following acute medical illness may be improved by screening for sex-specific predictors including perinatal mental health history.

The objective was to determine risk factors of psychiatric hospitalization among a Veterans Administration database of patients with dementia and comorbid bipolar disorder (D+BD). Patients with D+BD had a greater prevalence of psychiatric hospitalization (28% vs 4%). The strongest predictor of psychiatric hospitalization was the presence of an alcohol use disorder (51% risk); patients without alcohol use disorders but under the age of 70 had the next highest risk (33% risk). However, patients with an alcohol use disorder had shorter psychiatric hospitalizations than those without. Compared with patients without BD, D+BD patients were more likely to have alcohol use disorders (15% vs 3%) and any other substance use problem (10% vs 1%). In patients diagnosed with dementia and bipolar disorder, the strongest risk factor for psychiatric hospitalization was an alcohol abuse disorder. These findings suggest that disorders with increased frequency in BD affect the course of dementia.

Back to table of contents Previous article Next article Clinical Case ConferenceFull AccessSecondary Mania in Older AdultsJohn O. Brooks III, Ph.D., M.D., and Jennifer C. Hoblyn, M.D., M.P.H.John O. Brooks III, Ph.D., M.D., and Jennifer C. Hoblyn, M.D., M.P.H.Published Online:1 Nov 2005https://doi.org/10.1176/appi.ajp.162.11.2033AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail Although mania is commonly associated with bipolar disorder, it can have many etiologies (1). Thus, "primary mania" results from bipolar disorder, whereas "secondary mania" results from pharmacological, metabolic, or neurologic causes (1, 2). Older adults are at risk for secondary mania because of increased medical comorbidities and neurological changes. In one retrospective study of 50 patients with mania who were older than 65 years, it was the first manic episode for 28% of the patients and 71% had a comorbid neurological disorder (3).The etiology of mania is important because although acute symptomatic treatment of both primary and secondary mania may be similar, appropriate treatment of secondary mania includes addressing the cause (1). We present here two case histories of secondary mania in older adults, discuss their presentations and differential diagnosis in turn, and discuss treatment.Case 1Past HistoryMs. A, a 67-year-old married African American woman with no previous psychiatric history, was seen for an acute manic episode with psychotic symptoms. She had been in her usual state of health until 3 days before admission, when she developed an abnormally elated mood accompanied by delusions and racing thoughts.The patient's medical history was remarkable for a history of well-controlled hypertension, a resection of a left parieto-occipital meningioma, and a three-vessel coronary bypass graft for angina 4 years earlier. She reported two episodes of transient slurred speech, one just before the meningioma resection and the other 4 months before she was seen for the manic episode. Her usual medications included extended-release nifedipine (60 mg/day), ticlopidine (250 mg t.i.d.), and benazepril (20 mg/day).Present IllnessApproximately 3 weeks before her hospital admission, Ms. A reported that she had contracted an upper respiratory tract infection with a cough and had begun treatment with intermittent doses of pseudoephedrine, 60 mg, plus hydrocodone, 5 mg. Her infectious symptoms were not improving, so clarithromycin was added. After 7 days of clarithromycin therapy, Ms. A arose from her bed earlier than usual and announced to her daughter, "I feel free! I feel alive!" These statements were accompanied by an elated mood and an unprecedented interest in the Bible. The family reported this was a marked change, as Ms. A was typically rather quiet and reserved.Over the next 2 days, Ms. A became increasingly hyperverbal and would quote scripture while she ran through the house with her hands up in the air. She began frantically writing a lengthy and disorganized missive to God in which she apologized for past sins and transgressions. Her manic symptoms persisted and escalated to include emotional effusiveness, overfamiliarity, sleeplessness, and the development of delusions and auditory hallucinations. She asserted that she was receiving messages from Bob Hope through the television, appeared suspicious of family members when they expressed concern, and was unwilling to undergo an outpatient magnetic resonance imaging (MRI) scan because she thought she was under arrest. She described hearing voices of individuals from previous "waking" dreams. There was no history of confusion, disorientation, stereotyped motor activity, or changes in level of consciousness.Ms. A was first admitted to the neurology service for evaluation and management, and she was subsequently transferred to the inpatient psychiatry service. There were no remarkable physical or neurological findings. During the mental status examination Ms. A was noted to be an attentive, cooperative woman who appeared her stated age and had a lively, engaging demeanor and normal motor activity. Her speech was mildly pressured and tangential, requiring redirection to guide her back to the question. She described herself as "better than ever—excellent," and her affect was congruent with her mood. She described ideas of reference in that characters on television shows were making special references to her recent religious enlightenment. She denied further auditory hallucinations or paranoid delusions. Notably, her cognitive abilities were not impaired, and she scored 28 out of 30 on the Mini-Mental State Examination (MMSE) (4), although she exhibited some errors on confrontation naming, e.g., "tie" for a "tassel."Ms. A's serum chemistry, cerebrospinal fluid and cultures, urinalysis, blood cultures, and chest X-ray were unremarkable. The hematology profile was notable for a mild normocytic anemia with a hematocrit of 33.0 ml/dl. Her erythrocyte sedimentation rate was slightly elevated at 48 mm/hour. Her level of thyroid-stimulating hormone was low at 0.23 μU/ml (normal=0.39–0.45) with a normal free T4 level. A brain computed tomography (CT) scan showed evidence only of her past meningioma resection. A brain MRI revealed encephalomalacia related to the previous surgery as well as abnormal hyperintensities in the brain stem, periventricular matter, and deep white matter. These hyperintensities most likely represented chronic ischemic changes. An electroencephalogram (EEG) showed slow sharp waves in the area of the surgical resection but no epileptiform activity or other abnormal patterns.Low-dose haloperidol was administered from the beginning of Ms. A's stay in the psychiatry unit and was tapered off by the time of discharge. Throughout her hospital stay, her manic and psychotic symptoms gradually dissipated. At the time of discharge, Ms. A was taking clonazepam, 0.5 mg b.i.d., which was tapered and discontinued after discharge. Her family members reported that her disposition at the time of discharge was somewhat brighter than her baseline but not remarkably so.DiscussionAlthough bipolar disorder can have a late onset in persons over the age of 50 without a previous psychiatric history or a family history of bipolar disorder (5–8), new-onset mania in older adults is most commonly secondary (1, 2). Mania in older adults tends to be more debilitating than in younger adults, as evidenced by the lower scores on the Global Assessment Scale scores of older manic patients (9). In addition, patients whose first manic episode is after the age of 58 exhibit increased cognitive impairment, which is partially reversible (9, 10). Thus, it is important to rule out delirium and dementia. Mania is typically characterized by an abnormally elevated or irritable mood lasting at least 1 week. It may be accompanied by one or more of the following: grandiosity, decreased need for sleep, increased talkativeness, flight of ideas, distractibility, increased goal-directed activity, psychomotor agitation, and excess involvement in potentially harmful activities, all of which lead to a marked decrease in the level of functioning. These features distinguish themselves from delirium, in which the cardinal feature is a waxing and waning alteration in consciousness accompanied by a change in cognition (e.g., disorientation or memory or language disturbances). The symptoms of delirium may be accompanied by changes in affect, such as anxiety and fear. Differentiation between the two is accomplished by longitudinal observation as well as monitoring for affective changes. This patient had manic symptoms without any waxing or waning of consciousness or other evidence of delirium, which suggests a diagnosis of mania.The cognitive dysfunction that often accompanies mania in older adults (11) may suggest a diagnosis of dementia. However, there are differences in the presentations and premorbid histories of dementia and mania. Agitation and psychosis in dementia are typically phenomena that occur later in the course of illness, rather than in the initial presentation (12, 13). Agitation without psychosis occurs in dementia and may be manifest as "sundowning," which is commonly defined as increased agitation and restlessness beginning in the late afternoon and extending to early evening (14).Most important, dementia would likely be preceded by changes in cognitive abilities in the absence of affective symptoms. The cognitive changes of dementia usually occur over years, in contrast to those of mania, which are abrupt and accompanied by affective symptoms. After a period of agitation, the cognitive abilities of the demented patient may improve slightly but will still be markedly impaired, given the likely advanced stage of dementia. The nondemented manic patient would tend to recover mostly from the cognitive impairment (15). Comprehensive neuropsychological testing of Ms. A was not performed because of her relatively normal score on the MMSE. It is interesting that Ms. A did not exhibit the pronounced cognitive deficits described by Young (11). Had she exhibited such deficits, dementia would have been ruled out on the basis of her premorbid history.Because Ms. A had a history of a meningioma resection, it is possible that her mania was related to seizure activity. Mania may occur in epileptic patients during interictal periods and can last up to 8 weeks (16). This finding highlights the fact that mania in epilepsy need not be associated with the disturbances of a seizure but perhaps the brain insult itself. For Ms. A, seizure would be a reasonable avenue to pursue because there were several factors that could have given rise to epileptic foci. Her meningioma resection could provide such a focus, although its occipital location makes it unlikely that a related seizure would give rise to her behavioral changes. Epileptic foci can originate from stroke—a very real possibility in this older patient with a history of vascular disease, cardiac bypass surgery, and two possible transient ischemic attacks. Neuroimaging studies, however, did not reveal any evidence of stroke, nor did the EEG reveal any epileptiform activity.Although Ms. A and her family reported no history of falls, she was taking nifedipine, ticlopidine, and benazepril. All of these agents are capable of causing hypotensive episodes. If Ms. A had an episode of orthostasis, she may have fallen and sustained a head injury. Indeed, in a 1-year follow-up study of 66 subjects with closed-head injuries, 9% experienced manic episodes, and many of them had basal temporal lesions (17). Damage to the hypothalamus has been associated with lasting, rapidly fluctuating moods (18). Mania after head injury has mostly been described in case reports after closed-head injuries and postsurgical intervention for subdural hematomas. In one case series, the average onset of mania after head injury was 2.8 years, with a range of 0–12 years, and irritable euphoria and assaultive behavior were common symptoms (19). Some researchers have found a preponderance of right-sided lesions following mania related to head injury (20), but there have been isolated case reports of mania following left hemispheric lesions (21). The CT showed no evidence of contusion or skull fracture for Ms. A.It was important to rule out endocrine disorders in this older female patient, as endocrine abnormalities, such as thyroid disorders, should be considered in older patients with acute mental status changes. Classically, hypothyroidism is associated with mental slowing and depression, but it can lead to florid psychosis (22), as can hyperthyroidism (23, 24). It is interesting that the degree of hypothyroidism appears to be unrelated to the degree of psychiatric symptoms in patients who are psychotic because of hypothyroidism (25).Antibiotics can cause mania in older adults, which raised the possibility that clarithromycin was the source of Ms. A's mania. For this reason, her clarithromycin was stopped at admission. There are several reports of secondary mania apparently induced by clarithromycin (26–30). This could be a side effect of this class of medications (albeit an infrequent one), as other macrolides have been reported to be associated with mania (27). Older adults may be more vulnerable to such effects not only because they are more likely to receive antibiotics but also because slower P450 microenzyme metabolism could result in higher plasma levels of the drug. For example, older adults metabolize clarithromycin more slowly than do younger adults (31, 32). The mechanism behind antibiotic-induced mania is unclear but could be related to γ-aminobutyric acid (GABA) antagonism. There is evidence that ciprofloxacin is a GABA antagonist (33). Clarithromycin may have led to CNS disinhibition brought about by GABA antagonism, but we know of no documentation of GABA antagonism by clarithromycin.The short-term treatment of Ms. A required only low-dose haloperidol and clonazepam. As her symptoms subsided, both of these medications were tapered and discontinued. Because the presumptive etiological agent, clarithromycin, was removed, Ms. A did not require continuing therapy with a mood stabilizer.Case 2Past HistoryMr. B, a 60-year-old man with no past psychiatric history, was involuntarily admitted after being seen in a clinic with insomnia, increased energy level, pressured speech, tangential thinking, and grandiose delusions. He had been married and divorced twice, with no children, and was living alone in his own home. He was employed as a freelance sports journalist. Although he claimed to have unusually close relationships with several women, there was no evidence so support this claim; he did not meet criteria for a diagnosis of erotomania. On a recent business trip he spent several hundred dollars on clothing to "catch the ladies' eyes" and had his eyebrow and tongue pierced as he thought this would make him more attractive.Mr. B had been diagnosed with hypertension but was untreated. He acknowledged episodes of depression in the past, but none had required hospitalization. He denied abuse of alcohol or illicit substances in the past, and the only remarkable aspect of his family psychiatric history was that his brother was diagnosed with panic disorder.Present IllnessMr. B was admitted to the inpatient psychiatry service, where he continued to display manic symptoms for approximately 4 days while his medication doses were being titrated, all the while requesting a "decongestant for the brain." His speech was pressured with some clanging, and his affect was superficial, dysphoric, and tearful at times. Mr. B felt he possessed special powers; he claimed that he was a "sounder," which he described as a person who can see into the future, and that he had the ability to "run the United Nations." He stated that his powers "make quantum leaps look like picnics." His rapid thought processes led him to feel that the rest of the world was slow, to the point that he felt telephones dialed too slowly. At times Mr. B experienced auditory hallucinations of music and television commercials.The results of serum chemistries, a complete blood count, liver function tests, and thyroid function tests were all within normal limits. The results of a fluorescent treponema antibody absorption test and a urine drug screen were negative.During a workup for his manic episode, a CT scan revealed a right-sided heterogenous, partially cystic, and calcified mass in the medial aspect of the right temporal lobe. Differential diagnosis included a giant aneurysm dermoid/epidermoid lesion, a glioma, and a nerve sheath tumor, such as a meningioma or an atypical schwannoma. An MRI with gadolinium performed 2 days later revealed a well-circumscribed extra-axial mass 3.4 cm (anterior-posterior) by 3.0 cm (transverse) by 3.0 cm (craniocaudal), which extended into the right foramen ovale, medial to the right temporal lobe (Figure 1). The neurosurgery service was consulted and opted to debulk the tumor in approximately 2 months.Mr. B's drug doses were titrated to 20 mg/day of olanzapine and 1500 mg b.i.d. of divalproex sodium. By the ninth day of his hospitalization he insisted on being discharged to his own home with outpatient follow-up. His mental status examination was markedly improved with euthymic mood, no abnormal movements, and logical and goal-directed thought processes, without psychosis or thoughts of harming himself or others.Follow-UpMr. B underwent a right pterional craniotomy, and the mass was resected. The psychiatry consultation service followed him closely during his hospital stay. Postoperatively his recovery was complicated by pneumonia and some dysphagia. He was treated with several antibiotics and transferred to the rehabilitation medicine service, where his mental status continued to improve.DiscussionOlder patients with new-onset mania include individuals who have a history of depression as well as those without any past psychiatric history (34). It was possible that Mr. B's clinical picture was one of first-episode mania in bipolar disorder. However, as in case 1, it was important to rule out other contributing factors.For a 60-year-old man with impulsive behaviors (piercing his eyebrow and tongue), one should consider the possibility of substance abuse even though the patient may deny it, as this patient did. Although substance abuse is often associated with younger adults, it must be ruled out in older adults with mania (5). Although we know of no specific data regarding the incidence of substance-induced manic syndromes among older adults, older adults are likely more sensitive to the effects of illicit substances, such as amphetamines, methamphetamine, and cocaine. We did not find any evidence of substance abuse in this patient.Although Mr. B had a history of depressed mood, he was not taking an antidepressant. If he had been, it would have been important to bear in mind that several psychotropic medications can cause mania. Indeed, some researchers have found that older adults are more likely to have initial manic episodes from antidepressant therapy than are younger adults (35). Tricyclic antidepressants have long been recognized as a risk factor for secondary mania (36). The mechanism underlying this association is unknown but could be related to noradrenergic activity. Venlafaxine, which is a norepinephrine reuptake inhibitor at higher doses (37), has been associated with mania (38). However, some selective serotonin reuptake inhibitors, such as paroxetine (39) and fluoxetine (40), have been associated with manic episodes in younger adults yet have relatively little norepinephrine reuptake inhibition (37). Thus, mania may be induced by receptor activity that is not related to antidepressant action.Paradoxically, several atypical antipsychotics (olanzapine, risperidone, quetiapine, and ziprasidone), which are approved for treatment of bipolar disorder and/or mania, have been associated with mania (41). In a critical review of 33 reported cases, Rachid et al. (41) concluded that there was "strong evidence" to support a causal link. They discussed the hypothesis that secondary mania induced by atypical antipsychotics may reflect potent blockade of serotonin 5-HT2A but not dopamine D2 receptors. This pattern of receptor activity could presumably lead to frontal disinhibition.In a review of 50 consecutive psychiatric admissions for mania of people over the age of 65, Tohen et al. (3) found that 12 of 14 cases of first-episode mania were related to a neurological disorder or infection, most commonly stroke. Fujikawa et al. (44) also suggested that most cases of secondary mania in older adults result from stroke. However, the incidence of poststroke mania is low and has been estimated at 1% of all strokes (43). We considered the possibility that Mr. B had had a stroke in light of his untreated hypertension, although in the absence of any focal deficits this would be unlikely. Indeed, there was no evidence of stroke on the CT or MRI.In the course of the neurological workup for Mr. B, the right-sided mass was discovered. Older adults with new-onset mania are more than twice as likely to have an underlying neurological disorder as are older bipolar patients who have had many manic episodes (3, 44). Although mania is not a common presentation of cerebral tumors, of six patients who developed mania either before or after the removal of a tumor, five had tumors that were frontal or temporal in location and often in the right hemisphere (45). This patient's right-sided tumor is in keeping with these observations.As Mendez (46) discussed, a variety of brain lesions have been reported as correlates of mania. Bilateral orbitofrontal and right temporoparietal (47, 48), right basal and medial temporal lobe (49), basal ganglia (50), thalamic (51), and right frontotemporal (52) lesions have all been associated with mania. A young patient with bilateral dorsomedial thalamic lesions exhibited a secondary mania, and a single photon emission computed tomography (SPECT) study revealed hypoperfusion of the bilateral prefrontal regions (53). Subcortical arteriosclerotic encephalopathy (Binswanger's disease) led to first-episode mania in a 65-year-old man (54). Subcortical hyperintensities have been reported in geriatric patients with mania (11). Jorge et al. (17) found that temporal basal polar lesions were a commonality underlying secondary mania after traumatic brain injury. Jorge et al. reported that this association was significant even after they accounted for lesions in other areas of the brain.The exact mechanism by which brain insult leads to mania is unclear, although there is evidence of associations between right-sided lesions and mania (46, 55). Fenn and George (56) reported an instance in which a left-sided temporal infarct preceded the first episode of mania in a 78-year-old man. Several researchers have argued that right orbitofrontal damage is the sine qua non of secondary mania (45, 48, 57). Case reports of mania associated with other lesions are consistent with the argument for right orbitofrontal damage, in that there could be disruption of the pathways between limbic or prefrontal areas and other deeper structures, such as the basal ganglia, thalamus, and hypothalamus (50, 58).Treatment ConsiderationsThe symptomatic treatment of secondary mania in older adults is relatively similar to the treatment of primary mania, but proper treatment demands a determination of the etiology of secondary mania. Here we shall discuss treatment options for behavioral management of acute mania in older adults. Regardless of the agent used, secondary mania typically does not require prophylaxis, as does primary mania.For acute agitation associated with secondary mania, benzodiazepines and antipsychotics are reasonable choices. Benzodiazepines may be used in the treatment of acute agitation associated with secondary mania, but one must use them cautiously in older adults. Aging tends to slow the oxidative metabolic pathways in the liver, so benzodiazepines that are metabolized through conjugated processes, which are not impaired, are preferred. Thus, a shorter-acting benzodiazepine that is metabolized conjugatively, such as lorazepam, would be a suitable choice.Atypical antipsychotics lessen many of the complications of typical antipsychotics, but they can cause sedation. Although the Food and Drug Administration (FDA) does not differentiate between primary and secondary mania, it seems reasonable to use atypical antipsychotics while bearing in mind the recent FDA warning regarding death and atypical antipsychotics in older adults. The consensus guidelines on the use of antipsychotics for older adults suggest that a preferred treatment of mania is an atypical antipsychotic and a mood stabilizer (52). Further, the consensus guidelines indicate that the preferred medications could be chosen from risperidone, quetiapine, and olanzapine and, in some instances, aripiprazole as well (52). The major factors influencing selection are the presence of complicating medical conditions, such as constipation, diabetes, etc.Mood stabilizers, such as divalproex sodium or lithium, are viable treatment options but tend to have more side effects for older adults. Unfortunately, both medications can cause sedation and nausea. Lithium can be especially problematic in older patients because they are more likely to take nonsteroidal antiinflammatory drugs as well, which would reduce the renal clearance of lithium. Moreover, lithium can lead to hypothyroidism. Older adults are often more sensitive to side effects of medications than are younger adults, so doses should be lowered accordingly. Mania associated with structural central nervous system disease may respond better to valproate or carbamazepine (59). To our knowledge, the newer anticonvulsant agents topiramate and lamotrigine have not been studied in this particular patient population (59), and lamotrigine is less desirable because of its protracted titration period. Overall, unless the patient has hepatic failure, divalproex is a reasonable choice for treatment when a mood stabilizer is needed.ConclusionsSecondary mania in older adults is a serious medical condition that requires a comprehensive differential diagnosis. Older adults are more susceptible to disorders that can lead to secondary mania, so a thorough past psychiatric history is essential. Late-onset bipolar disorder is possible, but it is not the most likely etiology in older adults (3). New-onset mania in older adults calls for neuroimaging studies to rule out tumor and stroke as causes. Pharmacological treatment of the acute condition is largely the same as for primary mania but with doses lower than those for younger adults because of older adults' slower metabolism and sensitivity to side effects (9). Because secondary mania generally does not require prophylactic treatment, it is questionable whether treatment with divalproex, lithium, or carbamazepine is necessary. Fortunately, the majority of deficits that accompany secondary mania in older adults resolve if the etiology is determined and treated.Received Feb. 4, 2005; revision received May 23, 2005; accepted May 27, 2005. From the Psychiatry Service, Palo Alto VA Health Care System, Palo Alto, Calif.; and the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine. Address correspondence and reprint requests to Dr. Brooks, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305; [email protected] (e-mail). The authors thank Stephanie Woodard for her assistance with the manuscript.Figure 1. MRI of the Brain Showing a Right-Sided Mass in a 60-Year-Old Man With Secondary ManiaReferences1.. Krauthammer C, Klerman GL: Secondary mania: manic syndromes associated with antecedent physical illness or drugs. Arch Gen Psychiatry 1978; 35:1333–1339Crossref, Medline, Google Scholar2.. Hoblyn JC, Brooks JO: Herbal supplements in older adults: consider interactions and adverse events that may result from supplement use. Geriatrics 2005; 60:18, 22–23Google Scholar3.. Tohen M, Shulman KI, Satlin A: First-episode mania in late life. Am J Psychiatry 1994; 151:130–132Link, Google Scholar4.. Folstein MF, Folstein SE, McHugh PR: "Mini-Mental State": a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975; 12:189–198Crossref, Medline, Google Scholar5.. Depp CA, Jin H, Mohamed S, Kaskow J, Moore DJ, Jeste DV: Bipolar disorder in middle-aged and elderly adults: is age of onset important? J Nerv Ment Dis 2004; 192:796–799Crossref, Medline, Google Scholar6.. Depp CA, Jeste DV: Bipolar disorder in older adults: a critical review. Bipolar Disord 2004; 6:343–367Crossref, Medline, Google Scholar7.. Almeida OP, Fenner S: Bipolar disorder: similarities and differences between patients with illness onset before and after 65 years of age. Int Psychogeriatr 2002; 14:311–322Crossref, Medline, Google Scholar8.. Moorhead SR, Young AH: Evidence for a late onset bipolar-I disorder sub-group from 50 years. J Affect Disord 2003; 73:271–277Crossref, Medline, Google Scholar9.. Young RC, Klerman GL: Mania in late life: focus on age at onset. Am J Psychiatry 1992; 149:867–876Link, Google Scholar10.. Mirchandani IC, Young RC: Management of mania in the elderly: an update. Ann Clin Psychiatry 1993; 5:67–77Crossref, Medline, Google Scholar11.. Young RC: Geriatric mania. Clin Geriatr Med 1992; 8:387–399Crossref, Medline, Google Scholar12.. Lopez OL, Becker JT, Sweet RA, Klunk W, Kaufer DI, Saxton J, Habeych M, DeKosky ST: Psychiatric symptoms vary with the severity of dementia in probable Alzheimer's disease. J Neuropsychiatry Clin Neurosci 2003; 15:346–353Crossref, Medline, Google Scholar13.. Schneider LS, Dagerman KS: Psychosis of Alzheimer's disease: clinical characteristics and history. J Psychiatr Res 2004; 38:105–111Crossref, Medline, Google Scholar14.. Volicer L, Harper DG, Manning BC, Goldstein R, Satlin A: Sundowning and circadian rhythms in Alzheimer's disease. Am J Psychiatry 2001; 158:704–711Link, Google Scholar15.. Martínez-Arán A, Vieta E, Reinares M, Colom F, Torrent C, Sanchez-Moreno J, Benabarre A, Goikolea JM, Comes M, Salamero M: Cognitive function across manic or hypomanic, depressed, and euthymic states in bipolar disorder. Am J Psychiatry 2004; 161:262–270Link, Google Scholar16.. Kudo T, Ishida S, Kubota H, Yagi K: Manic episode in epilepsy and bipolar I disorder: a comparative analysis of 13 patients. Epilepsia 2001; 42:1036–1042Crossref, Medline, Google Scholar17.. Jorge RE, Robinson RG, Starkstein SE, Arndt SV, Forrester AW, Geisler FH: Secondary mania following traumatic brain injury. Am J Psychiatry 1993; 150:916–921Link,

OBJECTIVE:Off-label prescribing of medications, polypharmacy, and other questionable prescribing practices have led investigators to examine a large VA pharmacy database to determine if physician prescribing decisions appear reasonable. METHOD:The current study addresses the question of physician prescribing of atypical antipsychotics in 34,925 veterans with schizophrenia, using a series of signal detection analyses. RESULTS:These results suggest that only three factors (hospital size, age, and secondary diagnosis) allow classification of patients prescribed atypicals into three groups with frequencies of use of atypicals ranging from 43% to 79%, and that these results are consistent with reasonable clinical practice. CONCLUSIONS:Results of two-stage signal detection analyses are readily interpretable by clinicians and administrators who are faced with the task of evaluating how physicians prescribe medications in clinical practice. Physicians' decisions to prescribe atypical antipsychotics are based on both patient and fiscal considerations. This likely reflects a combination of clinical judgment and institutional guidelines.

Objectives: To evaluate the impact of external memory devices on the efficacy of a package of internal mnemonic techniques. Participants wrote two types of lists during the study phase: (a) a list of study words and/or (b) a loci list. At recall, participants were not allowed to refer to either of the lists they had written during the study. Design: 2 x 2 factorial with writing study words ("write" or "not write") and writing down a previously established loci list ("write" or "not write") manipulated as between-participants variables. Participants: 68 community-dwelling adults 55 years of age and older who wished to improve their memory. Measurements: Free word recall. Results: There were statistically significant effects of writing the loci list, but not of writing the list of study words. Scores were higher when participants wrote the loci lists compared to when they did not. Conclusions: Use of external mnemonics may enhance the efficacy of internal mnemonics, even when the external mnemonic is not used at the time of recall.

We compared the efficacy of sleep restriction therapy combined with sleep hygiene, nap modification of sleep restriction therapy combined with sleep hygiene, and sleep hygiene alone as treatments for insomnia in 39 community-dwelling men and women 55 years and older. We used the wrist actigraph as an objective outcome measure for all subjects at baseline, end of treatment, and 3-month follow-up; polysomnography (PSG) was conducted in a subgroup of subjects. Although subjects appeared to follow restriction instructions through follow-up, we found few between-group differences in treatment efficacy. Lack of treatment effect might be explained by the efficacy of HYG as a treatment in itself and the relatively low symptom level in these healthy older poor sleepers. At baseline, actigraphic results were found to correlate more highly than sleep log data with PSG in our sample. Actigraphic total sleep time, in particular, was highly correlated with PSG. ( J Geriatr Psychiatry Neurol 2000; 13:17-27).

The objective of this work was to study the differences in performance on a nonauditory memory task between older volunteers with and without hearing impairment. The design was cross-sectional. Three-hundred-forty-four community-dwelling adults aged 55 to 93 years, who volunteered for a mnemonic training class served as participants. Participants' hearing was tested with a Maico MA-27 portable audiometer. The dependent measure was performance on a visually presented serial word recall test. Participants were also asked to report whether they had a problem with their hearing. Hearing impairment was associated with poor performance on a serial word recall task, even after controlling for age-related differences on that task. Hearing acuity appears to be related to serial word recall in older adults. Because auditory presentations were not involved, this relation raises the question of whether hearing loss may be concomitant with other changes that affect cognitive abilities.

The pattern of deterioration in patients with Alzheimer's disease is highly variable within a given population. With recent speculation that the apolipoprotein E allele may influence rate of decline and claims that certain drugs may slow the course of the disease, there is a compelling need for sound statistical methodology to address these questions. Current statistical methods for describing decline do not adequately take into account between-patient variability and possible floor and/or ceiling effects in the scale measuring decline, and they fail to allow for uncertainty in disease onset. In this paper, the authors analyze longitudinal Mini-Mental State Examination scores from two groups of Alzheimer's disease subjects from Palo Alto, California, and Minneapolis, Minnesota, in 1981-1993 and 1986-1988, respectively. A Bayesian hierarchical model is introduced as an elegant means of simultaneously overcoming all of the difficulties referred to above.

OBJECTIVES:To identify profiles of subjects who respond to mnemonic training for serial word and proper name recall.DESIGN:Analysis of J. O. Brooks et al.'s (1999) mnemonic training data using Quality Receiver Operating Characteristic (QROC) and longitudinal regression analyses (LRA).SETTING:Community.PARTICIPANTS:224 community-dwelling adults 55 years of age and older who wished to improve their memory.MEASUREMENTS:Performance on serial word and proper name tests; performance on cognitive ability tests.RESULTS:Although the QROC and LRA identified several common predictors (baseline performance, mental rotation ability, and paired associate learning), the QROC identified additional predictors and cognitive ability profiles associated with successful response.CONCLUSIONS:Similar degrees of response to mnemonic training are associated with heterogeneous cognitive profiles. This finding highlights the fact that participants rely on a variety of abilities to derive benefit from mnemonic training and thus suggests different avenues from which to approach this training.

Objectives : To improve performance with mnemonic techniques for remembering words and proper names. Design : For word recall, a 2 × 2 factorial in which type of pretraining and length of training were between-subjects manipulations. For proper name recall, a two-group design in which type of pretraining was manipulated between subjects. Setting : Community. Participants : 268 community-dwelling adults over the age of 55 years who wished to improve their memory. Measurements : Recall of words and proper names both before and after training in mnemonics. Intervention : Participants received a 2-week training course on two mnemonic techniques, the method of loci for words and a name association technique for proper names. Results : There was no effect of the pretraining manipulation on proper name recall. For word recall, however, a multiple regression that included age indicated that the older-old participants benefited more from a combination of comprehensive pretraining and extended mnemonic training than did the younger-old. Conclusions : Increased training time coupled with a comprehensive pretraining regimen can improve the performance of the older-old in using mnemonics; this improved performance cannot be attributed solely to enhanced knowledge of the mnemonic.

OBJECTIVES:To assess the longitudinal effects of acety-L-carnitine (ALC) on patients diagnosed with Alzheimer's disease.DESIGN:Longitudinal, double-blind, parallel-group, placebo-controlled.SETTING:Twenty-four outpatient sites across the United States.PARTICIPANTS:A total of 334 subjects diagnosed with probable Alzheimer's disease by NINCDS-ADRDA criteria. These data were originally reported by Thal and colleagues (1996).MEASUREMENTS:Cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS) given every 3 months for 1 year.RESULTS:The average rate of change was estimated using the trilinear approach, which allows for periods of both change and stability. Both the ALC group and the placebo group exhibited the same mean rate of change on the ADAS (0.68 points/month). However, a multiple regression analysis revealed a statistically significant Age x Drug interaction characterized by younger subjects benefiting more from ALC, significant, cutpoint for ALC benefit was 61 years of age.CONCLUSIONS:ALC slows the progression of Alzheimer's disease in younger subjects, and the use of the trilinear approach to estimate the average rate of change may prove valuable in pharmacological trials.

The authors propose that meta-analysts explicitly specify their research question and their standards for adequate studies to be included, using whatever standards they would have applied had they been asked to peer-review the individual studies for funding. Such a proposal corresponds to previous ones with regard to considerations of sampling, measurement, design, and analysis adequacy, but the authors of this study extend the proposal to the inclusion of the definition of adequate power. They show that if adequate power is defined and then used in reviewing studies for inclusion in a meta-analysis, excluding those that are by the meta-analysts' own criterion "underpowered," this strategy would go far toward removing bias due to the "file-drawer problem" and resulting misleading research conclusions.

Department of Psychiatry and Behavioral Sciences, Stanford University, Palo Alto, California, U.S.A

Subtypes of Alzheimer disease (AD) can be approached from different ways. An intuitive and commonly proposed subtype relates to the age at onset of disease. Research on age at onset as a subtype has yielded conflicting results that may, in part, reflect different measurement approaches. Refinement of the measurement of change in AD should yield a clearer picture of subtypes, as would closer ties between neuropathologic and clinical work. Thus, it is suggested that future research should use measurement techniques that more closely characterize AD than do current approaches. In addition, progress would likely be through attempts to link clinical findings regarding rates of change to neuropathologic findings.