High-dose armodafinil in treatment-refractory bipolar depression.

BACKGROUND: Bipolar depression is a serious neuropsychiatric disorder associated with a high risk of morbidity and suicidality. Standard antidepressants approved for treating major depressive disorder fail to exert efficacy in bipolar depression. Although 5 agents have been developed for the treatment of bipolar depression, treatment resistance is still observed in some patients, and requires off-label pharmacotherapy. Modafinil and armodafinil have been reported to improve treatment-resistant bipolar depression, but with inconsistent results. METHODS: We present a case of a 65-year-old woman with severe bipolar depression who failed to respond to electroconvulsive therapy and IV ketamine but later responded to high-dose armodafanil. RESULTS: The patient responded to high-dose armodafinil (gradually titrated to 1,000 mg/d) and achieved remission with good tolerability for 5 years. Recently, she contracted COVID-19 and developed muscular weakness. After a lengthy workup, we became concerned for myopathy as an adverse effect from armodafinil. The patient's dose of armodafinil was significantly reduced and she subsequently became very depressed and functionally disabled before improving again when armodafinil 1,000 mg/d was reinstated. CONCLUSIONS: We propose that some of the negative results seen in research of armodafinil for bipolar depression may be due to the use of low doses (100 to 200 mg/d), and higher doses may be needed for adequate response in treatment-resistant bipolar depression.

Measurement-based care training curriculum in psychiatry residency programs: I: Description of the curriculum and demonstration of implementation.

BACKGROUND: Recent literature shows that most practicing psychiatrists do not receive training in measurement-based care (MBC). Among the primary barriers to MBC implementation are the lack of formal training and curriculums. We present the first comprehensive MBC curriculum for use in adult psychiatric practice, and describe how the curriculum is adapted and implemented in psychiatry residency training programs. METHODS: The Standard for Clinicians' Interview in Psychiatry (SCIP) was developed as a measurement-based care tool for clinicians' use. The SCIP is the only instrument that includes 18 reliable and validated clinician-rated scales covering most adult psychiatric disorders. The SCIP has simple, unified rules of measurement that apply to the 18 scales. The MBC curriculum includes 2 instruction manuals, 4 didactic lectures, and 12 videotaped interviews. We describe the annual learning and implementation of MBC curriculum in residency programs. RESULTS: The curriculum implementation at West Virginia University and Delaware Psychiatric Center began in 2019 and is ongoing. We present 3 case demonstrations of the implementation of MBC in clinical settings. CONCLUSIONS: Comprehensive implementation of MBC curriculum in residency programs has the potential to facilitate research and create a "culture" of MBC in future generations of psychiatrists.

Aripiprazole lauroxil 2-month formulation with 1-day initiation in patients hospitalized for an acute exacerbation of schizophrenia: exploratory efficacy and patient-reported outcomes in the randomized controlled ALPINE study.

BACKGROUND: A randomized, controlled, phase 3b study (ALPINE) evaluated efficacy and safety of a 2-month formulation of aripiprazole lauroxil (AL) using a 1-day initiation regimen in patients hospitalized for an acute exacerbation of schizophrenia. Paliperidone palmitate (PP) was used as an active control. Exploratory endpoint assessments included severity of illness, positive and negative symptoms, quality of life, caregiver burden, and satisfaction with medication. METHODS: Adults were randomly assigned to AL 1064 mg q8wk or PP 156 mg q4wk as inpatients, discharged after 2 weeks, and followed through week 25. Exploratory efficacy measures included the 3 original PANSS subscales, Clinical Global Impression-Severity (CGI-S) subscale, and caregiver Burden Assessment Scale. Exploratory patient-reported outcomes (PROs) included the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF) and the Medication Satisfaction Questionnaire. Within-group changes from baseline through week 25 were analyzed for AL and PP separately. PROs were summarized based on observed data. RESULTS: Of 200 patients randomized (AL, n = 99; PP, n = 101), 99 completed the study (AL, n = 56; PP, n = 43). For AL, PANSS subscale and CGI-S scores improved from baseline through week 25 (mean [SE] change from baseline at week 25: Positive, -7.5 [0.70]; Negative, -3.9 [0.46]; General, -11.8 [0.83]; CGI-S, -1.3 [0.12]). Caregiver burden also improved (mean [SD] changes from baseline at week 9: -8.4 [10.15]; week 25: -8.9 [12.36]). Most AL patients were somewhat/very satisfied with treatment at each timepoint (70.8%-74.7%); mean Q-LES-Q-SF total scores were stable in the outpatient period. For PP, results were similar: PANSS Positive, -7.3 (0.67); Negative, -3.6 (0.69); General, -10.9 (1.22); CGI-S, -1.4 (0.16); caregiver burden, week 9: -8.8 (11.89) and week 25: -9.2 (14.55); satisfaction with treatment, 64.7%-69.3%; and stable Q-LES-Q-SF scores. CONCLUSIONS: ALPINE patients initiating the 2-month AL formulation using the 1-day initiation regimen as inpatients and continuing outpatient care experienced schizophrenia symptom improvement, sustained patient satisfaction with medication, stable quality of life, and reduced caregiver burden. A similar benefit pattern was observed for PP. These results support the feasibility of starting either long-acting injectable in the hospital and transitioning to outpatient treatment. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03345979 [trial registration date: 15/11/2017].

The effects of yoga on depression and motor function in patients with Parkinson's disease: A review of controlled studies.

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative/neuropsychiatric disorder characterized by both motor and non-motor symptomology. The reported prevalence of depression in patients with PD is difficult to ascertain due to overlapping somatic symptoms and failure to self-report symptoms. Although antidepressants remain a first-line treatment, they can have adverse effects. Recently, literature has demonstrated that due to its anti-inflammatory properties, yoga may be an effective nonpharmacologic therapy for depression. METHODS: A search was conducted to identify randomized controlled trials (RCTs) published from January 2000 to January 2019 that assessed the effects of yoga on depression and motor functioning in PD. RESULTS: Three studies met the criteria for inclusion. In one RCT, biweekly yoga resulted in a decrease in depression score (P = .056). In another RCT, weekly yoga resulted in a significant decrease in depression and demonstrated that its therapeutic effects are long-lasting. Finally, in a third RCT, no significant difference was found between control and experimental groups in depression after biweekly yoga. However, yoga was found to be protective against worsening of depression. CONCLUSIONS: Our review suggests that the practice of yoga may be a useful nonpharmacologic adjunctive treatment for depression in patients with PD. However, more controlled RCTs are needed to validate our conclusions.

White matter pathology in patients with borderline personality disorder: A review of controlled DTI studies.

BACKGROUND: Neuroimaging, especially diffusion tensor imaging (DTI), has emerged as a helpful tool in assessing and characterizing white matter (WM) integrity. The resultant early treatment from early diagnosis is crucial because treatment is often more efficacious. Borderline personality disorder (BPD) is a challenging disorder to diagnose and treat, and has been reported to have various neurobiologic abnormalities. We conducted a search of the literature to review WM pathology findings in BPD. METHODS: A search was conducted to identify systematic reviews and meta-analyses published from January 2000 to September 2019 that assessed WM integrity in BPD. RESULTS: Four studies were included. One study demonstrated no difference in WM between BPD and healthy controls. Another study found decreased fractional anisotropy (FA) within the corpus callosum (CC) and orbitofrontal regions. A subsequent randomized controlled trial reported a decrease in FA within the fornix, CC, and right superior/anterior corona radiata with associated increase in radial diffusivity in the left anterior thalamic radiation. The fourth study found a decrease in the axial diffusivity within the cingulum, inferior longitudinal fasciculus, and inferior frontoccipital fasciculus. CONCLUSIONS: Our review concludes that BPD is associated with measurable WM pathology. Methods such as DTI might emerge as useful tools in the management of BPD. More controlled studies are needed to validate our conclusions.

A systematic review of diffusion tensor imaging studies in drug-naïve OCD patients before and after pharmacotherapy.

BACKGROUND: Obsessive-compulsive disorder (OCD) is difficult to treat. Studies have shown associations of white matter pathology in OCD, as well as various other psychiatric illnesses, using diffusion tensor imaging (DTI). We conducted a systematic review of controlled studies on drugnaïve patients with OCD vs pharmacologically treated patients with OCD to examine whether pharmacotherapy exerts changes on white matter in OCD. METHODS: A search was conducted to identify controlled trials published from January 2010 to July 2018. All studies used DTI to assess for white matter volume in drug-naïve patients with OCD, pharmacologically treated patients with OCD, and healthy controls. RESULTS: Three studies met the criteria for inclusion. The findings of one study suggest that selective serotonin reuptake inhibitors do exert some changes on white matter, some of which appear to reverse abnormalities noted in the fronto-striato-thalamo-cortical pathways. In another study, no differences in white matter parameters were found between drug-naïve patients vs healthy controls. In a third study, high fractional anisotropy in the splenium correlated with a greater severity of OCD. CONCLUSIONS: Our systematic review suggests mixed results regarding whether drug-naïve patients with OCD have a difference in white matter compared with pharmacologically treated patients with OCD, and whether patients with OCD have a difference in white matter compared with healthy controls.

A focus on postpartum depression among African American women: A literature review.

BACKGROUND: Some studies have reported a higher rate of postpartum depression in African American vs White women. We reviewed the literature to identify the possible factors associated with a greater risk of postpartum depression in African American women. METHODS: A comprehensive literature review was conducted using journal databases such as PubMed and Google Scholar. Keywords used in the search included postpartum depression, ethnicity, and race. Using the PRISMA (Preferred reporting items for systematic reviews and meta-analysis) method for review articles, 8 studies were identified and included. RESULTS: We identified 8 studies that met the criteria for our review. Most of the studies showed that African American and Hispanic women had a higher odds ratio of reported postpartum depression due to lack of social support, access, trust, past depression, and other factors. However, 1 study found that although African Americans are more likely to report symptoms of postpartum depression, they are less likely to seek treatment due to cultural stigma regarding mental illness. CONCLUSIONS: The data we reviewed confirm the ethnic differences in postpartum depression. Addressing the factors involved will lead to better health outcomes for both mothers and their children.

Low high-density lipoprotein and psychopathology: A review.

BACKGROUND: An association between the level of total cholesterol and psychopathology has been the focus of numerous studies. Low total cholesterol has been found to be related to depression, personality disorders, and dissociative disorder. High cholesterol has been associated with schizophrenia, obsessive-compulsive disorder (OCD), panic disorder, generalized anxiety disorder, and posttraumatic stress disorder. However, no reviews of the psychiatric correlates of high-density lipoprotein (HDL) have been published. We reviewed the literature for studies reporting a significant association between low or high levels of HDL and psychopathology. METHODS: A search of major databases (PubMed and CINAHL) was conducted using the following keywords: HDL, depression, anxiety, schizophrenia, OCD, and psychiatric disorders. RESULTS: Eight studies met our search criteria. Six of the 8 studies reported significantly higher rates of depression, anxiety, suicide attempts, and violent behaviors in participants with low HDL. CONCLUSIONS: Overall, a low HDL may not only be associated with risk for cardiac disease, but also with increased risk for serious psychiatric disorders. Further controlled studies are warranted.

Changes in inflammatory biomarkers before and after SSRI therapy in PTSD: A review.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are regarded as the standard pharmacotherapy for the treatment of posttraumatic stress disorder (PTSD). Recent studies indicate that neuroinflammation is associated with PTSD. We conducted a search of the literature to determine if SSRI efficacy is associated with a decrease in inflammation levels. METHODS: A literature search was conducted to identify studies published from January 2000 to January 2019 that measured changes in inflammatory biomarkers before and after SSRI treatment in patients with PTSD. RESULTS: Four studies met the criteria for inclusion. In one study, SSRI use significantly reduced interleukein-1beta. An open trial of paroxetine found a significant decline in cortisol. In a third study, paroxetine treatment in patients with PTSD and depression showed no significant changes in cortisol. Finally, analysis of cerebrospinal fluid in patients with PTSD showed no significant changes in corticotropin-releasing factor, interleukin-6, brain-derived neurotrophic factor, or insulin-like growth factor 1. Substance P was found to be decreased. CONCLUSIONS: Our review had mixed results regarding whether SSRI therapy for PTSD is associated with a reduction in inflammation. These findings may be due to the heterogeneity of PTSD. More randomized controlled trials are needed due to the potential benefits of SSRIs for reducing inflammation in patients with PTSD (as has been reported in depression studies).

Bidirectional relationship between transient ischemic attacks and depression: A review.

BACKGROUND: An association between cerebrovascular events and psychiatric disorders has been reported. However, the focus has centered on stroke, and there has been a lack of attention to a possible relationship between transient ischemic attacks (TIAs) and depression. METHODS: We conducted a review of studies that looked specifically at the risk of depression after TIAs and the risk of TIAs in patients with depression. A total of 8 studies were identified, 4 examining the occurrence of depression following a TIA, and 4 examining the occurrence of TIAs after the onset of depression. RESULTS: There was a bidirectional effect: 3 of 4 studies showed an increased risk of TIAs in patients with depression, and 4 of 4 studies found an increase of depression following a TIA. The percentage of patients having a TIA from the pool of patients with depression was 3.18%. The percentage of patients who developed depression after a TIA in the pooled samples was 6.88%. CONCLUSIONS: Both depression and TIAs are serious medical disorders and they appear to have a bidirectional relationship. Further clinical and neurobiological studies in this area are warranted.

Long-term safety and tolerability of aripiprazole lauroxil in patients with schizophrenia.

OBJECTIVE: Safety and tolerability of long-term treatment with the long-acting antipsychotic aripiprazole lauroxil (AL) were evaluated in patients with schizophrenia. METHODS: This was an international, multicenter, phase 3, 52-week safety study of 2 fixed doses of AL (441 mg or 882 mg intramuscular every 4 weeks). Safety endpoints included adverse events (AEs) and extrapyramidal symptoms (EPS) including akathisia, injection-site reactions (ISRs), and clinically relevant changes in metabolic and endocrine values. RESULTS: Of 478 patients entering this study, 236 (49%) continued from a previous 12-week, phase 3 efficacy study of AL, and 242 (51%) were newly enrolled. Overall, 77% and 23% of patients received AL 882 mg (N = 368) and 441 mg (N = 110), respectively. AEs occurred in 50.4% of patients; most were mild (28.7%) or moderate (18.2%). The most common AEs were insomnia (8.4%) and increased weight (5.0%). Akathisia was reported as an AE in 3.8% of the overall population, with higher rates in patients initiating AL on study entry than those continuing on AL. EPS-related AEs occurred in 9.4% of patients, and AEs related to metabolic parameters were reported in 4.6% of patients. Weight gain was minimal (0.8 kg), and no clinically relevant changes were observed for metabolic parameters. The overall incidence of ISRs was 3.8%; most were associated with the initial injections in patients receiving their first injection in this study. CONCLUSION: Long-term treatment with AL is generally well tolerated, with a safety profile consistent with that of oral aripiprazole. It is a suitable option for patients with schizophrenia.

The use of memantine in neuropsychiatric disorders: An overview.

BACKGROUND: Memantine is a non-competitive N-methyl-d-aspartate receptor antagonist currently used for the treatment of Alzheimer's disease as an approved indication. However, as knowledge of signaling pathways is increasing, the therapeutic potential of memantine is being applied for the treatment of various psychiatric illnesses. METHODS: The PubMed online database was searched for the use of memantine in various psychiatric disorders. Case studies, open-label trials, and controlled trials from the search were included. RESULTS: Memantine monotherapy was found to exert efficacy in several neuropsychiatric conditions, including autism spectrum disorder, binge eating disorder, and attention-deficit/hyperactivity disorder. For posttraumatic stress disorder and generalized anxiety disorder, memantine was found efficacious in augmentation with other medications. In obsessive-compulsive disorder (OCD), memantine was used as both an augmentation to selective serotonin reuptake inhibitors and standalone therapy, and most published studies found it to improve OCD symptoms. For schizophrenia, memantine has been reported to be consistently effective for negative symptoms only. The manic phase of bipolar disorder also appears to benefit from memantine. The depressive phase of bipolar disorder and major depressive disorder did not respond significantly to memantine. Catatonia as a symptom of various disorders improved in several case studies when memantine was used in combination with other medications. CONCLUSIONS: Memantine may have several therapeutic applications in psychiatry, reflecting the involvement of glutamate pathways in multiple psychiatric disorders.

Effects of nonpharmacological therapies on anxiety and cortisol: A meta-analysis.

BACKGROUND: Although pharmacotherapy is considered the standard of care for the treatment of anxiety, a subset of the patients remains resistant or intolerant to iatrogenic adverse effects. Nonpharmacological and nonpsychotherapeutic interventions, sometimes referred to as "complementary treatments," have emerged as possible alternatives in the treatment of anxiety. We conducted a meta-analysis of placebo-controlled studies to assess the efficacy of nonpharmacological therapy on anxiety. In addition, because serum and salivary cortisol levels are elevated during anxiety, we conducted a separate meta-analysis of pre- and posttreatment cortisol levels. METHODS: A search was conducted to identify randomized controlled trials published from January 2010 to May 2017 that measured the effects of nonpharmacological therapies on State Trait Anxiety Index (STAI) scores and cortisol levels before and after treatment. RESULTS: Four studies met the criteria for inclusion. Our meta-analysis reveals that participants receiving nonpharmacological therapy had a statistically significant decrease in STAI scores (d = -.340; 95% confidence interval [CI], -.639, -.041; P = .026), but no statistically significant decrease in cortisol levels (d = -.085; 95% CI, -.396, .226; P = .591) after intervention. CONCLUSIONS: Our meta-analysis data suggest that "complementary" therapies improved the clinical manifestations of anxiety and thus may be useful as adjunctive approaches to drug treatment.

Body temperature rises following improvement of depression with ECT.

BACKGROUND: Recent studies have reported hyperthermia is an efficacious treatment for depression. Thus, we hypothesized that a proven depression therapy such as electroconvulsive therapy (ECT) would be associated with an increase in body temperature. METHODS: A retrospective chart analysis was conducted on 33 participants who recovered from depression after a course of ECT. All were hospitalized for recurrent, severe symptoms and had no previous ECT treatment. Oral temperature recordings before and after the first and last ECT treatments were collected for each participant. Statistical analysis was performed using paired t test. RESULTS: No significant change in mean oral temperature occurred after the first ECT, but a significant increase from baseline was observed after the final ECT treatment when depression symptoms had clinically remitted (P < .009). CONCLUSIONS: Improvement in clinical depression with ECT is correlated with an increase in body temperature. Body temperature may have potential as a biomarker for ECT efficacy, and possibly for antidepressant pharmacotherapies.

Effect of aripiprazole lauroxil in patients with acute schizophrenia as assessed by the Positive and Negative Syndrome Scale-supportive analyses from a Phase 3 study.

OBJECTIVE: Aripiprazole lauroxil (AL) is a long-acting injectable atypical antipsychotic that was evaluated for the treatment of schizophrenia in a randomized, placebo-controlled, Phase 3 study. Here, we present exploratory analyses of supportive efficacy endpoints. METHODS: Patients experiencing an acute exacerbation of schizophrenia received AL 441 mg intramuscularly (IM), AL 882 mg IM, or matching placebo IM monthly. Supportive endpoints included changes from baseline at subsequent time points in Clinical Global Impression-Severity (CGI-S) scale score; Positive and Negative Syndrome Scale (PANSS) Total score; PANSS Positive, Negative, and General Psychopathology subscale scores; PANSS Marder factors (post hoc); and PANSS responder rate. Overall response rate, based on PANSS Total score and Clinical Global Impression-Improvement (CGI-I) scale score, was also analyzed. RESULTS: Of 622 patients who were randomized, 596 had ≥1 post-baseline PANSS score. Patients were markedly ill at baseline (mean PANSS Total scores 92-94). Compared with placebo, CGI-S scores; PANSS Positive, Negative, and General Psychopathology subscale scores; and PANSS Marder factors were all significantly (p<0.001) improved by Day 85 with both AL doses, with significantly lower scores starting from Day 8 in most instances. Treatment response rates were significantly (p<0.001) greater with both doses of AL vs placebo. CONCLUSION: AL demonstrated robust efficacy on CGI-S score, PANSS subscale scores, PANSS Marder factors, and response rates. Study limitations included use of a fixed dose for initial oral aripiprazole and fixed monthly AL doses without the option to individualize the oral initiation dosing or injection frequency for efficacy, tolerability, or safety.

Guidance for switching from off-label antipsychotics to pimavanserin for Parkinson's disease psychosis: an expert consensus.

Patients with Parkinson's disease psychosis (PDP) are often treated with an atypical antipsychotic, especially quetiapine or clozapine, but side effects, lack of sufficient efficacy, or both may motivate a switch to pimavanserin, the first medication approved for management of PDP. How best to implement a switch to pimavanserin has not been clear, as there are no controlled trials or case series in the literature to provide guidance. An abrupt switch may interrupt partially effective treatment or potentially trigger rebound effects from antipsychotic withdrawal, whereas cross-taper involves potential drug interactions. A panel of experts drew from published data, their experience treating PDP, lessons from switching antipsychotic drugs in other populations, and the pharmacology of the relevant drugs, to establish consensus recommendations. The panel concluded that patients with PDP can be safely and effectively switched from atypical antipsychotics used off label in PDP to the recently approved pimavanserin by considering each agent's pharmacokinetics and pharmacodynamics, receptor interactions, and the clinical reason for switching (efficacy or adverse events). Final recommendations are that such a switch should aim to maintain adequate 5-HT2A antagonism during the switch, thus providing a stable transition so that efficacy is maintained. Specifically, the consensus recommendation is to add pimavanserin at the full recommended daily dose (34 mg) for 2-6 weeks in most patients before beginning to taper and discontinue quetiapine or clozapine over several days to weeks. Further details are provided for this recommendation, as well as for special clinical circumstances where switching may need to proceed more rapidly.

The Efficacy of Buprenorphine in Major Depression, Treatment-Resistant Depression and Suicidal Behavior: A Systematic Review.

Although several pharmacological options to treat depression are currently available, approximately one third of patients who receive antidepressant medications do not respond adequately or achieve a complete remission. Thus, novel strategies are needed to successfully address those who did not respond, or partially respond, to available antidepressant pharmacotherapy. Research findings revealed that the opioid system is significantly involved in the regulation of mood and incentives salience and may be an appropriate target for novel therapeutic agents. The present study aimed to systematically review the current literature about the use of buprenorphine (BUP) for major depression, treatment-resistant depression (TRD), non-suicidal self-injury (NSSI) behavior, and suicidal behavior. We investigated Pubmed and Scopus databases using the following keywords: "buprenorphine AND depression", "buprenorphine AND treatment resistant depression", "buprenorphine AND suicid*", "buprenorphine AND refractory depression". Several evidence demonstrate that, at low doses, BUP is an efficacious, well-tolerated, and safe option in reducing depressive symptoms, serious suicidal ideation, and NSSI, even in patients with TRD. However, more studies are needed to evaluate the long-term effects, and relative efficacy of specific combinations (e.g., BUP + samidorphan (BUP/SAM), BUP + naloxone (BUP/NAL), BUP + naltrexone) over BUP monotherapy or adjunctive BUP treatment with standard antidepressants, as well as to obtain more uniform guidance about the optimal BUP dosing interval.

Multiple neurotoxic effects of haloperidol resulting in neuronal death.

BACKGROUND: Several published studies have reported an association between antipsychotic medications, especially first-generation agents, and a decline in gray matter volume. This prompted us to review the possible neurotoxic mechanisms of first-generation antipsychotics (FGAs), especially haloperidol, which has been widely used over the past several decades. METHODS: A PubMed search was conducted using the keywords haloperidol, antipsychotic, neurotoxicity, apoptosis, oxidative stress, and neuroplasticity. No restrictions were placed on the date of the articles or language. Studies with a clearly described methodology were included. RESULTS: Animal, cell culture, and human tissue studies were identified. Thirty reports met the criteria for the search. All studies included haloperidol; a few also included other FGAs (fluphenazine and perphenazine) and/or second-generation agents (SGAs) (aripiprazole, paliperidone, and risperidone). A neurotoxic effect of haloperidol and other FGAs was a common theme across all studies. Minimal (mainly at high doses) or no neurotoxic effects were noted in SGAs. CONCLUSIONS: A review of the literature suggests that haloperidol exerts measurable neurotoxic effects at all doses via many molecular mechanisms that lead to neuronal death. A similar effect was observed in 2 other FGAs, but the effect in SGAs was much smaller and occurred mainly at high doses. A stronger binding to serotonin 5HT-2A receptors than to dopamine D2 receptors may have a neuroprotective effect among SGAs. Further studies are warranted to confirm these findings.

The intense desire for healthy limb amputation: A dis-proprioceptive neuropsychiatric disorder.

BACKGROUND: The first mention of a condition in which apparently nonpsychotic individuals have a strong, unrelenting desire to amputate ≥1 of their healthy limbs was published nearly 4 decades ago. Once dismissed as a paraphilia, the condition in recent years has been re-investigated with neurologic testing and imaging, yielding evidence suggesting it may be attributable to a neuroanatomical anomaly. METHODS: A literature review of data was conducted of recently published studies with pinprick testing, magnetic resonance imaging (MRI)/functional MRI imaging, magnetoencephalography, and interviews of individuals with a desire for limb amputation. RESULTS: Published literature on this condition features studies with a limited number of participants. However, the results indicate that affected individuals predominantly desire amputation of the left lower limb, and correspondingly, usually have changes in cortical thickness in the right parietal lobe. CONCLUSIONS: Further investigation of this condition is warranted, particularly, more research into the precise nature of the anomalous neuroanatomy, biopsychosocial background of those with the condition, and longitudinal perspective of the childhood onset and evolution of symptoms. Large sample studies involving a collaborative effort across multiple sites are required.