Vaccines for COVID-19.

Since the emergence of COVID-19, caused by the SARS-CoV-2 virus at the end of 2019, there has been an explosion of vaccine development. By 24 September 2020, a staggering number of vaccines (more than 200) had started preclinical development, of which 43 had entered clinical trials, including some approaches that have not previously been licensed for human vaccines. Vaccines have been widely considered as part of the exit strategy to enable the return to previous patterns of working, schooling and socializing. Importantly, to effectively control the COVID-19 pandemic, production needs to be scaled-up from a small number of preclinical doses to enough filled vials to immunize the world's population, which requires close engagement with manufacturers and regulators. It will require a global effort to control the virus, necessitating equitable access for all countries to effective vaccines. This review explores the immune responses required to protect against SARS-CoV-2 and the potential for vaccine-induced immunopathology. We describe the profile of the different platforms and the advantages and disadvantages of each approach. The review also addresses the critical steps between promising preclinical leads and manufacturing at scale. The issues faced during this pandemic and the platforms being developed to address it will be invaluable for future outbreak control. Nine months after the outbreak began we are at a point where preclinical and early clinical data are being generated for the vaccines; an overview of this important area will help our understanding of the next phases.

Relationship between asthma and cognition: the Cooper Center Longitudinal Study.

BACKGROUND: Minimal data are available on the relationship between asthma and cognitive performance. In this report, we examine the relationship between asthma and cognitive performance in older adults, a subpopulation with elevated risk of cognitive impairment. METHODS: We conducted a cross-sectional, retrospective analysis of 1380 participants age ≥55 who completed preventive health examinations at the Cooper Clinic in Dallas, TX. Cognition was assessed using the Montreal Cognitive Assessment (MoCA), a brief test for mild cognitive impairment. Data were analyzed in a multiple logistic regression using MoCA scores suggestive of cognitive impairment as the dependent variable. RESULTS: When controlling for demographic characteristics, self-rated health status, inhaled corticosteroid use, and FEV1 /FVC, asthma were associated with 78% increased risk of cognitive impairment (P = 0.02) as defined by MoCA score. CONCLUSIONS: In the largest sample examined to date, we have identified a significant relationship between asthma and cognitive impairment in older people.

Prevalence of mood disorders and relationship to asthma severity in patients at an inner-city asthma clinic.

BACKGROUND: Depressive symptoms are associated with noncompliance and even sudden death in asthma patients. Some studies suggest that low-income, minority, inner-city asthma patients may be at high risk for asthma-related morbidity and mortality in which depression may be a risk factor. Minimal data are available on the prevalence of depression and other mood disorders in asthma patients. OBJECTIVE: In this pilot study, we examined the prevalence of depression and the association between depression and measures of asthma severity in patients at an inner-city asthma clinic. METHODS: Mood disorders were diagnosed using a diagnostic interview given to patients (N = 44) at asthma clinic visits. Inhaled steroid dose, FEV1 percentage, and asthma severity were also obtained. RESULTS: Eighteen patients (41%) had a lifetime mood disorder but only seven of these patients received pharmacotherapy. Patients with a past mood disorder had significantly higher FEV1 percentage predicted values (P = 0.03) than those without a mood disorder. Trends toward less severe asthma (P = 0.13) and lower inhaled steroid dose (P = 0.13) in patients with a mood disorder history were also found. CONCLUSIONS: The data suggest that mood disorders are common, but often unrecognized and untreated in asthma patients. The data also suggest that mood disorders are not necessarily associated with more severe asthma, at least in the population studied.

Atypical antipsychotics in bipolar and schizoaffective disorders.

No data are available comparing the relative efficacy of different atypical agents in patients with bipolar disorder. A chart review of bipolar and schizoaffective disorder patients who had received courses of at least two atypical agents (n = 33) in a community psychiatry system was conducted. No differences in rates of hospitalizations were found between individual atypical agents or between atypical agents as a class and conventional neuroleptics. However, a significant reduction in rates of emergency room visits was found with atypical agents compared to conventional neuroleptics, with a trend toward greater reduction with clozapine compared to other atypical antipsychotics. Larger prospective studies are needed to confirm these preliminary observations.

Ketoconazole in bipolar patients with depressive symptoms: a case series and literature review.

BACKGROUND: Data from several studies suggest that medications, such as ketoconazole, which lower cortisol levels, may be effective for major depressive disorder (MDD). As with MDD, the manic, depressive, and mixed phases of bipolar disorder are frequently associated with elevated cortisol levels. The literature on the use of cortisol-lowering strategies in mood disorders is reviewed, and a case series illustrating the use of ketoconazole in bipolar depression is presented. METHODS: For the review, the MEDLINE and PSYCHINFO databases were searched, as were the bibliographies of pertinent articles to find papers on the use of cortisol-lowering agents in patients with mood disorders. In our open-label case series (n = 6), ketoconazole (up to 800 mg/day) as an add-on therapy was given to patients with treatment-resistant or intolerant bipolar I or II disorders with current symptoms of depression. RESULTS: Several case reports and small open studies suggest that cortisol-lowering agents may be useful for patients with depression. Two recent placebo-controlled trials of ketoconazole on patients with MDD report conflicting results. In our case series, all three patients who received a dose of at least 400 mg/day had substantial reductions in depressive symptoms. None had significant increases in mania. However, cortisol levels were not lowered in any of the subjects. CONCLUSIONS: The literature suggests that cortisol-lowering medications may be effective for a subset of depressed patients. Our preliminary findings suggest that ketoconazole may be useful in some patients with bipolar depression. Larger clinical trials are needed to confirm our observations.

Efficacy of divalproex therapy for schizoaffective disorder.

Schizoaffective disorder is a common, severe, and lifelong illness; however, little is known about the pharmacologic treatment of this mental disorder. Divalproex has proven efficacy in the treatment of bipolar disorder. Therefore, to determine whether divalproex is also effective as adjunctive therapy for schizoaffective disorder, the authors performed a retrospective study of 20 patients in the public mental health system with schizoaffective disorder, bipolar type, who initiated divalproex therapy. The mean maximum dose of divalproex (+/-1 SD) was 1,150 mg (+/-400 mg; range, 500-2,000). The mean peak serum valproic acid level was 61 microg/mL (+/-25 microg/mL; range, 20-92). The overall improvement in Clinical Global Impression Scale scores was observed in 75% (15/20) of the patients (p = 0.0001). None in the sample worsened, and none discontinued divalproex because of side effects. These data suggest that divalproex is well-tolerated and effective as treatment of persistent schizoaffective disorder, bipolar type. Thus, divalproex may be an effective agent in the treatment of schizoaffective disorder as well as bipolar disorder. Controlled prospective trials in patients with schizoaffective disorder are needed to verify these findings.

Comparison of the internal state scale to clinician-administered scales in asthma patients receiving corticosteroid therapy.

Mood symptoms are reported frequently in asthma patients, particularly during corticosteroid therapy. This investigation compared the Internal State Scale (ISS), a self-report measure of symptoms of mania and depression, to the Hamilton Rating Scale for Depression (HRSD), Young Mania Rating Scale (YMRS), and Brief Psychiatric Rating Scale (BPRS) in a group of asthma patients (n=60 at baseline) before, during, and after a 1-2 week burst of prednisone. The depression and well being subscales of the ISS correlated well with HDRS scores. The perceived conflict subscale correlated with the BPRS scores. However, none of the ISS subscales correlated consistently and specifically with the YMRS in this population. Possible explanations for differences observed in bipolar versus asthma patients given the ISS are discussed. These data suggest the ISS may be a useful tool for depression symptoms and overall psychopathology in asthma patients and in patients receiving corticosteroid therapy. However, its ability may be attenuated outside of the population for which it was designed.

Open-label adjunctive topiramate in the treatment of bipolar disorders.

BACKGROUND: To preliminarily explore the spectrum of effectiveness and tolerability of the new antiepileptic drug topiramate in bipolar disorder, we evaluated the response of 56 bipolar outpatients in the Stanley Foundation Bipolar Outcome Network (SFBN) who had been treated with adjunctive topiramate in an open-label, naturalistic fashion. METHODS: In this case series, response to topiramate was assessed every 2 weeks for the first 3 months according to standard ratings in the SFBN, and monthly thereafter while patients remained on topiramate. Patients' weights, body mass indices (BMIs), and side effects were also assessed. RESULTS: Of the 54 patients who completed at least 2 weeks of open-label, add-on topiramate treatment, 30 had manic, mixed, or cycling symptoms, 11 had depressed symptoms, and 13 were relatively euthymic at the time topiramate was begun. Patients who had been initially treated for manic symptoms displayed significant reductions in standard ratings scores after 4 weeks, after 10 weeks, and at the last evaluation. Those patients who were initially depressed or treated while euthymic showed no significant changes. Patients as a group displayed significant decreases in weight and BMI from topiramate initiation to week 4, to week 10, and to the last evaluation. The most common adverse side effects were neurologic and gastrointestinal. CONCLUSIONS: These preliminary open observations of adjunctive topiramate treatment suggest that it may have antimanic or anticycling effects in some patients with bipolar disorder, and may be associated with appetite suppression and weight loss that is often viewed as beneficial by the patient and clinician. Controlled studies of topiramate's acute and long-term efficacy and side effects in bipolar disorder appear warranted.

Switching outpatients between atypical antipsychotics.

1. Some reports have suggested an increase in symptoms when switching patients with psychosis from clozapine to other atypical antipsychotics. 2. No data are available on switching between atypical antipsychotics other than clozapine, though this is common in clinical practice. 3. Six patients with schizophrenia or schizoaffective disorder, bipolar type were switched to quetiapine after finishing a clinical trial of sertindole. 4. During the observation period of two to ten weeks no subjects worsened and one improved. Side effects were mild. 5. These preliminary data suggest that switching between some atypical agents may be well tolerated. Larger controlled trials are needed to confirm this observation.

The psychiatric sequelae of civilian trauma.

Much of the literature on the psychiatric consequences of stress has focused on wartime combat trauma. However, traumatic events also frequently occur in civilian life. Controlled studies on the psychiatric effects of noncombat trauma were reviewed and a meta-analysis of these data was conducted. Generalized anxiety disorder (GAD), posttraumatic stress disorder (PTSD), substance abuse, phobia, and major depressive disorder (MDD) were significantly elevated compared with a pooled control group, whereas panic disorder and dysthymic disorder were not significantly increased. These data suggest that the psychiatric effects of civilian trauma include both anxiety and depressive disorders. The results are strikingly similar to those reported in combat veterans, suggesting that severe trauma, even in very different populations, may be associated with similar psychopathology.

Psychiatric diagnoses in inner city outpatients with moderate to severe asthma.

OBJECTIVE: Psychiatric symptoms may be associated with increased asthma morbidity and mortality. However, no investigations have identified syndromal psychiatric diagnoses in asthma patients using current diagnostic criteria or examined treatment received for mental illness. METHOD: We conducted structured clinical interviews on 32 patients with moderate to severe asthma to identify current and past psychiatric illness. RESULTS: Twenty-five percent of subjects had current major depressive disorder, but only 25 percent of these received antidepressants. Anxiety disorders, including panic disorder (16 percent), and social (13 percent) and specific phobias (28 percent) were also common. All subjects with panic disorder were receiving appropriate therapy. CONCLUSIONS: Asthma patients with moderate to severe asthma treated at community health facilities may have high rates of often untreated mood and anxiety disorders. Interventions aimed at identifying and treating psychiatric disorders in this population are needed.

Antidepressant-induced bruxism successfully treated with gabapentin.

BACKGROUND: Symptoms consistent with bruxism are a common chief complaint in dental practice. The authors describe a case of bruxism likely induced by the antidepressant venlafaxine and successfully treated with gabapentin. CASE DESCRIPTION: A case of bruxism, anxiety, insomnia and tremor is reported in a man with bipolar disorder that developed a few days after he initiated venlafaxine therapy for depression. The patient's psychiatrist prescribed gabapentin for anxiety symptoms, and shortly thereafter the man experienced a complete resolution of the bruxism. CLINICAL IMPLICATIONS: On the basis of this case and the available literature, the authors conclude that bruxism secondary to antidepressant therapy may be common. Thus, dentists should inquire about the use of these medications in patients who have bruxism. Gabapentin may offer promise in the treatment of this condition.

Hippocampal remodeling and damage by corticosteroids: implications for mood disorders.

Mood disorders are common, recurrent and disabling illnesses which are frequently associated with hypothalamic-pituitary-adrenal (HPA) axis dysregulation and memory loss. The hippocampus provides negative feedback to the HPA axis and has an important role in key aspects of spatial and declarative memory. Thus, hippocampal dysfunction could account for both the memory impairment and neuroendocrine abnormalities found in mood disorders. The critical role of the hippocampus in declarative memory, emotional processing, and vulnerability to stress has been demonstrated in both animal and human studies. Cellular processes in the hippocampus including long-term potentiation, neurogenesis, and dendritic remodeling are currently areas of intense study. Human studies report cognitive impairment consistent with hippocampal dysfunction in depression, bipolar disorder, Cushing's disease, and in those individuals receiving exogenous corticosteroids. This review examines data on the role of corticosteroids in hippocampal remodeling and atrophy in patients with mood disorders. Interventions to prevent or reverse the damaging effects of corticosteroids on the hippocampus are discussed.

Lamotrigine for the treatment of bipolar disorder: a clinical case series.

BACKGROUND: Recently, a number of new agents have become available to treat bipolar disorder, however many patients may not respond fully even when used in combination. Early reports in epilepsy studies suggested mood-related effects of lamotrigine treatment, as have preliminary reports in bipolar patients. METHODS: Seventeen patients meeting DSM-IV criteria for bipolar I (n = 9) or bipolar II (n = 8) disorder displaying affective symptoms and a past history of inadequate response or tolerability to at least two standard mood stabilizing agents were recruited through the Stanley Foundation Bipolar Network and treated with the new anticonvulsant lamotrigine in an add-on, open-label study. Response to therapy was assessed using the Clinical Global Impression Scale modified for bipolar disorder. RESULTS: The mean dose of lamotrigine was 187+/-157 mg/day (range 50-600 mg/day) for a mean duration of 159+/-109 days (range 14-455 days). Eleven (65%) patients were rated as very much or much improved. Lamotrigine was well tolerated, and may have mood stabilizing and antidepressant properties in some patients with bipolar disorder. LIMITATIONS: The study is hypothesis generating because it was uncontrolled and open. Controlled studies are warranted. CONCLUSIONS: This preliminary report supports clinical improvement for both mood cycling and depression in patients with bipolar disorder treated with lamotrigine.

Gabapentin in the acute treatment of refractory bipolar disorder.

BACKGROUND: Gabapentin, a new anti-epileptic agent, has been anecdotally reported to be effective in the treatment of mania. We systematically assessed the response rate in bipolar patients being treated adjunctively with gabapentin for manic symptoms, depressive symptoms, or rapid cycling not responsive to standard treatments. METHOD: Twenty-eight bipolar patients experiencing manic (n = 18), depressive (n = 5), or rapid-cycling (n = 5) symptoms inadequately responsive to at least one mood stabilizer were treated in an open fashion with adjunctive gabapentin. Illness response was assessed using the Clinical Global Impression Scale modified for bipolar disorder (CGI-BP). A 'positive response' was operationalized as a CGI response of much or very much improved. RESULTS: Fourteen of the 18 (78%) treated for hypomania or mania had a positive response to a dosage range of 600-3,600 mg/day. Patients with hypomania responded fastest, with a positive response achieved in 12.7 +/- 7.2 days. Patients with classic mania had a mean time to positive response of 25 +/- 12 days, and in patients with mixed mania it was 31.8 +/- 20.9 days. All of the five patients treated for depression had a positive response within 21 +/- 13.9 days. Only one of five patients with rapid cycling had a positive response. Gabapentin was well tolerated by all patients, with the most common side-effect being sedation. CONCLUSIONS: Gabapentin appears to have acute anti-manic and anti-depressant properties as an adjunctive agent for refractory bipolar illness. Prospective double-blind studies are needed to further delineate its acute efficacy when used as monotherapy and its prophylactic efficacy as monotherapy or in conjuction with other mood stabilizers.

The psychiatric side effects of corticosteroids.

LEARNING OBJECTIVES: Readers will learn the importance of psychiatric symptomatology with corticosteroid drug therapy, especially when combined with other medications. DATA SOURCES: A brief history of corticosteroid use over the last five decades was complied utilizing MEDLINE and PSYCHOINFO as sources of information which include peer-reviewed research articles, case studies, and relevant reviews in English. CONCLUSION: Corticosteroids are routinely prescribed for a variety of allergic and immunologic illnesses. Psychiatric side effects from corticosteroids include mania, depression and mood disturbances. Psychiatric symptoms usually occur within the first two weeks of corticosteroid therapy and seem to be dose related. Treatment with lithium or antipsychotics may be helpful. Physicians should carefully monitor patients for psychiatric and cognitive side effects of corticosteroid use.