Low and very low lithium levels: Thyroid effects are small but still require monitoring.

AIM: Low doses of lithium, as might be used for mood or dementia prevention, do not carry the same renal, toxicity, and tolerability problems of doses used for prophylaxis or treatment of mania. However, thyroid effects of low doses have not been investigated. Our goal in this study was to assess the changes in thyroid-stimulating hormone (TSH) associated with a broad range of lithium levels, including those well below the therapeutic range for bipolar disorders. METHODS: This study was conducted in a small healthcare system with 19 associated primary care clinics served by a Collaborative Care program of psychiatric consultation. In this retrospective review of electronic records, we searched for patients who had received a lithium prescription and both pre- and post-lithium thyroid-stimulating hormone (TSH) levels. RESULTS: Patients with low lithium levels (<0.5 mEq/L, N = 197) had a mean thyroid-stimulating hormone (TSH) increase of 0.52 mIU/L. Patients with maintenance lithium levels (0.5-0.8 mEq/L; N = 123) had a mean TSH increase of 1.01 mIU/L; and patients with antimanic lithium levels (>0.8 mEq/L; N = 79) had a mean TSH increase of 2.16 mIU/L. The probability of TSH exceeding the upper limit of normal in our laboratory (>4.2 mIU/L) was positively associated with pre-lithium TSH. CONCLUSION: These results suggest that the risk of lithium-induced hypothyroidism is dose-related, and relatively small with very low doses, but thyroid monitoring, including a pre-lithium TSH, is still warranted.

Lamotrigine and lithium in primary care psychiatric consultation: adoption and adverse effects.

BACKGROUND: The Collaborative Care Model of psychiatric consultation in primary care has improved outcomes for unipolar depression, but bipolar depressions are challenging for providers and consultants. Although lamotrigine and lithium are both first line medications for bipolar depression, their use in primary care has been declining over the last decade. OBJECTIVE: Our project aimed to quantify the frequency of and adoption of recommendations for lamotrigine and lithium, and their adverse effects, in a Collaborative Care program. METHODS: Chart review. RESULTS: For 620 depressed adult patients (Public Health Questionnaire, 9-item ≥10), lamotrigine and lithium were recommended by psychiatric consultant for 35% and 26% of patients, respectively; and when recommended, were prescribed by primary care providers 50% and 32% of the time, respectively. Eighty-four percent of lithium dosages were 600 mg or less; average serum level 0.32 mEq/l. In follow-up up to 6 months, lithium was associated with no more weight gain than lamotrigine; but 12% of patients receiving lithium had thyroid stimulating hormone increases exceeding the upper limit of normal, occurring in an average of 32 days after the initial prescription. CONCLUSIONS: (i) In a Collaborative Care program of psychiatric consultation, recommendations for lamotrigine and lithium were very frequent. (ii) Adoption of these recommendations is variable, warranting further investigation. (iii) Like higher doses, low doses of lithium induced hypothyroidism (rapidly)-but not weight gain.

Depression is a common problem. One variation, bipolar depression, often does not respond well to antidepressants. But bipolar depression is hard to diagnose, especially in busy primary care clinics. With too few psychiatrists available, primary care providers have often had to treat bipolar depression themselves. To address this problem, in the USA a system of consultation ('Collaborative Care') has been developed that allows a remote psychiatrist to make treatment recommendations for patients based on data gathered by the primary care team. In this study of 620 patients with depression, we looked at how often psychiatric consultants recommended two medications for bipolar depression which tend to be underused: lamotrigine and lithium. We found that lamotrigine was recommended for one third of these 620 patients, and lithium for one quarter­much higher percentages than are routine in primary care of depression. But because either the providers or their patients were hesitant about these medications, actual prescriptions were fewer: 50% of the times when it was recommended for lamotrigine; 32% for lithium. Side effects were few. This study shows that psychiatric consultation leads to increased use of important medications for bipolar depression. Now we need a study to show it helps improve outcomes!

The chronotherapeutic treatment of bipolar disorders: A systematic review and practice recommendations from the ISBD task force on chronotherapy and chronobiology.

AIMS: To systematically review the literature on the efficacy and tolerability of the major chronotherapeutic treatments of bipolar disorders (BD)-bright light therapy (LT), dark therapy (DT), treatments utilizing sleep deprivation (SD), melatonergic agonists (MA), interpersonal social rhythm therapy (IPSRT), and cognitive behavioral therapy adapted for BD (CBTI-BP)-and propose treatment recommendations based on a synthesis of the evidence. METHODS: PRISMA-based systematic review of the literature. RESULTS: The acute antidepressant (AD) efficacy of LT was supported by several open-label studies, three randomized controlled trials (RCTs), and one pseudorandomized controlled trial. SD showed rapid, acute AD response rates of 43.9%, 59.3%, and 59.4% in eight case series, 11 uncontrolled, studies, and one RCT, respectively. Adjunctive DT obtained significant, rapid anti-manic results in one RCT and one controlled study. The seven studies on MA yielded very limited data on acute antidepressant activity, conflicting evidence of both antimanic and maintenance efficacy, and support from two case series of improved sleep in both acute and euthymic states. IPSRT monotherapy for bipolar II depression had acute response rates of 41%, 67%, and 67.4% in two open studies and one RCT, respectively; as adjunctive therapy for bipolar depression in one RCT, and efficacy in reducing relapse in two RCTs. Among euthymic BD subjects with insomnia, a single RCT found CBTI-BP effective in delaying manic relapse and improving sleep. Chronotherapies were generally safe and well-tolerated. CONCLUSIONS: The outcome literature on the adjunctive use of chronotherapeutic treatments for BP is variable, with evidence bases that differ in size, study quality, level of evidence, and non-standardized treatment protocols. Evidence-informed practice recommendations are offered.

The ketogenic diet for type II bipolar disorder.

Successful mood stabilizing treatments reduce intracellular sodium in an activity-dependent manner. This can also be achieved with acidification of the blood, as is the case with the ketogenic diet. Two women with type II bipolar disorder were able to maintain ketosis for prolonged periods of time (2 and 3 years, respectively). Both experienced mood stabilization that exceeded that achieved with medication; experienced a significant subjective improvement that was distinctly related to ketosis; and tolerated the diet well. There were no significant adverse effects in either case. These cases demonstrate that the ketogenic diet is a potentially sustainable option for mood stabilization in type II bipolar illness. They also support the hypothesis that acidic plasma may stabilize mood, perhaps by reducing intracellular sodium and calcium.

Antidepressant Tapering Is Not Routine But Could Be.

INTRODUCTION: When antidepressants are discontinued, severe withdrawal symptoms are possible. Some patients have few or no problems stopping, whereas others struggle. That struggle can be minimized or prevented with careful dose tapering. How often is that done? METHODS: Using 7 years of medical records, we determined the percentage of patients who received a prescription for the lowest available dose of their antidepressant before it was discontinued, as an indicator of a deliberate taper. RESULTS: Over that period, 8.9% of patients had evidence of tapering. The percentage increased from 4.9% in 2014 to a plateau around 10% in the past 4 years. DISCUSSION: While reports of severe withdrawal are increasingly recognized and must be addressed, our data suggest that many patients can discontinue their antidepressants without a taper through the lowest dose. However, it is difficult to identify which patients will struggle without a careful taper. A "one-size-fits-all" taper approach is recommended, balancing the need for withdrawal prevention with the need to avoid unnecessary complexity for the majority of patients. The first decrement is key for all patients: it must go well. Thereafter many patients may accelerate but all should receive a prescription for the lowest available dose of their antidepressant.

A Prospective Analysis of Patient Characteristics Affecting the Outcome of Dorsal Splinting for Soft Tissue Mallet Injuries.

BACKGROUND: Much has been written about the diagnosis and treatment of soft tissue mallet injuries. However, there has been little regarding the characteristics of this injury affecting patients' prognosis. The purpose of this prospective study was to identify factors influencing the outcome of treatment of soft tissue mallet injuries. METHODS: Patients diagnosed with soft tissue mallet injuries were enrolled prospectively in a protocol of dorsal splinting for 6 to 12 weeks, followed by weaning over 2 weeks and then evaluated at 6, 9, and ≥12 months. RESULTS: Thirty-seven patients (38 digits) completed the study. Treatment success was defined as a final extensor lag of <15° and failure as a final extensor lag of ≥15°. Those failing splint treatment were older compared with those successfully treated. Patient compliance was significantly associated with a successful outcome. Factors that did not significantly affect success included time to treatment, initial injury severity, splinting duration, sex, and ligamentous laxity. Disabilities of Arm, Shoulder, and Hand scores >0 were not associated with treatment failure. Radiographic and clinical extension lag were statistically comparable. CONCLUSIONS: This study shows strong association between the success of splint treatment, younger patient age, and compliance with the treatment protocol. Despite this finding, most patients did not report any functional limitations, irrespective of the treatment success. In contrast to prior results, time to treatment and initial extensor lag did not significantly affect treatment success.

Clinical research diagnostic criteria for bipolar illness (CRDC-BP): rationale and validity.

BACKGROUND: In the 1970 s, scientific research on psychiatric nosology was summarized in Research Diagnostic Criteria (RDC), based solely on empirical data, an important source for the third revision of the official nomenclature of the American Psychiatric Association in 1980, the Diagnostic and Statistical Manual, Third Edition (DSM-III). The intervening years, especially with the fourth edition in 1994, saw a shift to a more overtly "pragmatic" approach to diagnostic definitions, which were constructed for many purposes, with research evidence being only one consideration. The latest editions have been criticized as failing to be useful for research. Biological and clinical research rests on the validity of diagnostic definitions that are supported by firm empirical foundations, but critics note that DSM criteria have failed to prioritize research data in favor of "pragmatic" considerations. RESULTS: Based on prior work of the International Society for Bipolar Diagnostic Guidelines Task Force, we propose here Clinical Research Diagnostic Criteria for Bipolar Illness (CRDC-BP) for use in research studies, with the hope that these criteria may lead to further refinement of diagnostic definitions for other major mental illnesses in the future. New proposals are provided for mixed states, mood temperaments, and duration of episodes. CONCLUSIONS: A new CRDC could provide guidance toward an empirically-based, scientific psychiatric nosology, and provide an alternative clinical diagnostic approach to the DSM system.

Bipolarity in a Collaborative Care Model Variation: Detection, Prevalence, and Outcomes.

OBJECTIVE: To assess the prevalence of bipolarity and its impact on clinical course, psychiatric consultants' diagnostic impressions and respective treatment outcomes were examined for patients with depression who were treated in a collaborative care model (CoCM) of psychiatric consultation. METHODS: Electronic records for 1,476 patients were reviewed for the presence of a mood disorder, which yielded 641 patients with complete data on several measures: the Composite International Diagnostic Interview, version 3.0 (CIDI); a questionnaire eliciting data on non-mania-related markers of bipolar disorder (family history, age of onset, course of illness, response to treatment); consultants' diagnostic impressions; and Patient Health Questionnaire-9 (PHQ-9) scores before and after consultation. RESULTS: Of referred patients, 97% were screened for bipolar disorder. A smooth distribution of scores on the CIDI was observed. Patients were divided into four groups on the basis of their CIDI scores (≥7, positive, or <7, negative) and on the consultant's recorded Impression (positive or negative for bipolarity). Of the study sample, 21% were CIDI positive (≥7), and 35% were Impression positive (sufficient bipolarity to guide treatment recommendations). All groups demonstrated equivalent decreases in PHQ-9 scores in the 6 months since consultation, including the potentially overdiagnosed group (CIDI negative, impression positive), which comprised 22% of the study sample. CONCLUSIONS: Universal screening for bipolarity in primary care is feasible in CoCM programs. Interpreting the data dimensionally is logical on the basis of the smooth distribution of CIDI scores. Such screening will yield high rates of bipolar disorder, much higher than previously reported. Offering treatment recommendations based on an impression of bipolarity to patients with negative CIDI results (<7) was not associated with outcomes worse than experienced by all other consultation patients. Multiple explanations of the latter finding are possible, warranting additional study.

Dark therapy for bipolar disorder using amber lenses for blue light blockade.

"Dark Therapy", in which complete darkness is used as a mood stabilizer in bipolar disorder, roughly the converse of light therapy for depression, has support in several preliminary studies. Although data are limited, darkness itself appears to organize and stabilize circadian rhythms. Yet insuring complete darkness from 6 p.m. to 8 a.m. the following morning, as used in several studies thus far, is highly impractical and not accepted by patients. However, recent data on the physiology of human circadian rhythm suggests that "virtual darkness" may be achievable by blocking blue wavelengths of light. A recently discovered retinal photoreceptor, whose fibers connect only to the biological clock region of the hypothalamus, has been shown to respond only to a narrow band of wavelengths around 450 nm. Amber-tinted safety glasses, which block transmission of these wavelengths, have already been shown to preserve normal nocturnal melatonin levels in a light environment which otherwise completely suppresses melatonin production. Therefore it may be possible to influence human circadian rhythms by using these lenses at night to blunt the impact of electrical light, particularly the blue light of ubiquitous television screens, by creating a "virtual darkness". One way to investigate this would be to provide the lenses to patients with severe sleep disturbance of probable circadian origin. A preliminary case series herein demonstrates that some patients with bipolar disorder experience reduced sleep-onset latency with this approach, suggesting a circadian effect. If amber lenses can effectively simulate darkness, a broad range of conditions might respond to this inexpensive therapeutic tool: common forms of insomnia; sleep deprivation in nursing mothers; circadian rhythm disruption in shift workers; and perhaps even rapid cycling bipolar disorder, a difficult- to -treat variation of a common illness.

Psychiatric consultation in the collaborative care model: The "bipolar sieve" effect.

Around the world, psychiatrists are in exceptionally short supply. The majority of mental health treatment is delivered in primary care. In the United States, the Collaborative Care Model (CCM) addresses the shortfall of psychiatrists by providing indirect consultation in primary care. A Cochrane meta-analysis affirms the efficacy this model for depression and anxiety. However, our experience with the CCM suggests that most patients referred for consultation have problems far more complex than simple depression and anxiety. Based on preliminary data, we offer five linked hypotheses: (1) in an efficient collaborative care process, the majority of mental illnesses can be handled by providers who are less expensive and more plentiful than psychiatrists. (2) A majority of the remaining cases will be bipolar disorder variations. Differentiating these from PTSD, the most common alternative or comorbid diagnosis, is challenging and often requires a psychiatrist's input. (3) Psychiatric consultants can teach their primary care colleagues that bipolar diagnoses are estimations based on rigorously assessed probabilities, and that cases fall on a spectrum from unipolar to bipolar. (4) All providers must recognize that when bipolarity is missed, antidepressant prescription often follows. Antidepressants can induce bipolar mixed states, with extreme anxiety and potentially dangerous impulsivity and suicidality. (5) Psychiatrists can help develop clinical approaches in primary care that identify bipolarity and differentiate it from (or establish comorbidity with) PTSD; and psychiatrists can facilitate appropriate treatment, including bipolar-specific psychotherapies as well as use of mood stabilizers.

The effects of sufentanil in the feline pulmonary vascular bed.

The purpose of this prospective vehicle controlled study was to test the hypothesis that sufentanil induces a depressor response in the pulmonary vascular bed of the cat and identify the receptors involved in the mediation or modulation of these effects. In separate experiments, the effects of diphenydramine (histamine receptor blocker), glibenclamide (ATP-sensitive K+ channel blocker), L-N5-(1-Iminoethyl) ornithine hydrochloride (L-NIO) (nitric oxide synthase inhibitor), nimesulide (selective cyclooxygenase (COX)-2 inhibitor), and naloxone (opiate receptor antagonist) were investigated on pulmonary arterial responses to sufentanil and other agonists in the feline pulmonary vascular bed. The lobar arterial perfusion pressures were continuously monitored, electronically averaged, and recorded. In the feline pulmonary vascular bed of the isolated left lower lobe, sufentanil induced a dose-dependent vasodepressor response that was not significantly altered after administration of glibenclamide, L-NIO, and nimesulide. However, the responses to sufentanil were significantly attenuated following administration of diphenhydramine and naloxone. The results of the present study suggest that sufentanil has potent vasodepressor activity in the pulmonary vascular bed of the cat and that this response may be mediated or modulated by both histaminergic and opioid receptor sensitive pathways.

Improving the diagnosis of bipolar disorder: predictive value of screening tests.

OBJECTIVE: To examine the impact of assumptions about prevalence or prior clinical probability of bipolar disorder on the clinical performance (predictive values) of diagnostic screening tests. METHOD: Sensitivity and specificity data from four reports on two bipolar screening instruments (the Mood Disorders Questionnaire and the Bipolar Spectrum Diagnostic Scale) were used to calculate positive and negative predictive values at varying prevalence levels. Bayesian statistical concepts were employed. RESULTS: At low prevalence or low prior clinical probability, the sensitivity and specificity of the test have little impact on negative predictive value; the tests perform well, with low risk of false negatives. Similarly, at low prevalence or low prior clinical probability, positive predictive values are low regardless of which sensitivity and specificity data are used: the risk of false positives is substantial. CONCLUSIONS: At lower prevalence or prior probabilities, as in the community or primary care setting, these screening tests can rule out bipolarity (when patients have insight into their symptoms), but do not effectively rule it in. Clinicians' estimates of prior probability have as much, or in many cases more, impact on the clinical performance of the bipolar screening tools than the tests' sensitivity and specificity. To improve the performance of screening tools, the primary emphasis needs to be placed on improving clinicians' skill at recognizing clinical and historical features of bipolar diagnosis.

An analysis of remifentanil in the pulmonary vascular bed of the cat.

In this investigation we sought to identify the role of remifentanil in the feline pulmonary vascular bed. Using adult mongrel cats in separate experiments, the effects of glibenclamide (adenosine triphosphate-sensitive K+ channel blocker), diphenhydramine (histamine H(1)-receptor antagonist), L-N5-(1-Iminoethyl) ornithine hydrochloride (nitric oxide synthase inhibitor), and naloxone (opioid receptor antagonist) were investigated in pulmonary arterial responses to remifentanil (opioid agonist), pinacidil (adenosine triphosphate-sensitive K+ channel activator), and bradykinin (nitric oxide synthase inducer). Under increased tone conditions in the isolated left lower lobe vascular bed of the cat, remifentanil induced a dose-dependent vasodepressor response that was not significantly altered after administration of glibenclamide and L-N5-(1-Iminoethyl) ornithine hydrochloride. Responses to remifentanil were significantly attenuated after administration of diphenhydramine and naloxone. The results suggest that remifentanil has potent vasodepressor activity in the feline pulmonary vascular bed and that these responses are mediated by histamine and opioid receptor sensitive pathways.

A case study of negative pressure wound therapy to manage acute necrotizing fasciitis.

Acute necrotizing fasciitis is a devastating infectious process that requires immediate surgical debridement. Intravenous antibiotic treatment, hyperbaric oxygen therapy, and wound management are considered the standard of care. Subsequent wound closure is achieved with split-thickness skin grafting, delayed surgical closure, or healing by secondary intention. When a patient refuses additional surgical treatment or is no longer a surgical candidate, as was the case with a patient who presented with acute necrotizing fasciitis caused by Clostridium perfringens in the upper extremity, secondary intention healing is the only treatment option. Following surgery and intravenous antibiotic treatment, her wounds were managed with topical negative pressure wound therapy. No adverse events occurred and the wounds were almost completely healed 63 weeks following surgery. Research to develop evidence-based protocols of care for the closure of these wounds is needed.

Agitated dysphoria after late-onset loss of response to antidepressants: a case report.

BACKGROUND: Antidepressants can sometimes cause agitation, particularly in patients with bipolar disorder, but concern about such effects is generally limited to the first weeks and months of treatment. METHOD: Demonstration of the occurrence of agitated dysphoria after loss of response to an antidepressant following continuous administration through 7 years of euthymia; with a worsening on dose increase; and recurrence of agitation on re-exposure 1 year later; in a patient whose previous dysthymia and recurrent depressions had no recognizable manic or hypomanic features. RESULTS: Only when the antidepressant was removed, twice, was treatment an atypical antipsychotic and lithium effective. CONCLUSION: An antidepressant which has been effective for as long as 7 years may still carry risk of inducing agitated dysphoria, even in apparently unipolar depression. In some patients, clinical vigilance for antidepressant-induced dysphoria may be warranted for extended periods of time.

Delayed union in internal fixation of pediatric both-bone forearm fractures.

The aim of this study was to retrospectively determine the risk factors for delayed union in 117 consecutive pediatric both-bone forearm fractures treated with internal fixation. Eight patients (7%, 8/117) had delayed unions, all were boys treated with intramedullary fixation for a fracture in the middle-third of the bone; and in seven patients, the ulna was the site of the delayed union. Older age, double-bone fixation, increased initial fracture displacement, and opening a closed ulna fracture were associated with longer time to union (P<0.05). Identification of risk factors will aid in the selection and duration of internal fixation and duration of immobilization.

An inexpensive family index of risk for mood issues improves identification of pediatric bipolar disorder.

Family history of mental illness provides important information when evaluating pediatric bipolar disorder (PBD). However, such information is often challenging to gather within clinical settings. This study investigates the feasibility and utility of gathering family history information using an inexpensive method practical for outpatient settings. Families (N=273) completed family history, rating scales, and the Mini-International Neuropsychiatric Interview (Sheehan et al., 1998) and the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children (Kaufman et al., 1997) about youths 5-18 (median=11) years of age presenting to an outpatient clinic. Primary caregivers completed a half-page Family Index of Risk for Mood issues (FIRM). All families completed the FIRM quickly and easily. Most (78%) reported 1+ relatives having a history of mood or substance issues (M=3.7, SD=3.3). A simple sum of familial mood issues discriminated cases with PBD from all other cases (area under receiver operating characteristic [AUROC]=.63, p=.006). FIRM scores were specific to youth mood disorder and not attention-deficit/hyperactivity disorder or disruptive behavior disorder. FIRM scores significantly improved the detection of PBD even controlling for rating scales. No subset of family risk items performed better than the total. Family history information showed clinically meaningful discrimination of PBD. Two different approaches to clinical interpretation showed validity in these clinically realistic data. Inexpensive and clinically practical methods of gathering family history can help to improve the detection of PBD.