Trazodone and Mianserin for Delirium: A Retrospective Chart Review.

BACKGROUND: Although antipsychotics are commonly used for delirium, their adverse effects are a serious concern in light of extrapyramidal symptoms and cardiovascular disturbances. In clinical practice, sedative antidepressants are frequently used as an alternative treatment for delirium; however, there is scarce evidence. Thus, we conducted a retrospective chart review to examine the use and effectiveness of trazodone and mianserin for delirium. METHODS: Patients who were admitted to a university hospital during 4 years and received either trazodone or mianserin on a regular schedule as monotherapy for the treatment of delirium were included. The rates of and times to the improvement of delirium were compared. RESULTS: Among 3971 patients who developed delirium, 379 (9.5%) and 341 (8.6%) patients received trazodone and mianserin on a regular schedule; 52 and 46 patients met the eligibility criteria (ie, monotherapy) for trazodone and mianserin, respectively. The percentages of patients 65 years or older were 86.5% (n = 45) for trazodone and 89.1% (n = 41) for mianserin. The rates of the improvement of delirium were 63.5% for trazodone and 50.0% for mianserin. Times to the improvement of delirium were 5.3 days (95% confidence interval, 3.2-7.4 days) for trazodone and 9.3 days (95% confidence interval, 5.3-13.3 days) for mianserin. There were no significant differences in the primary outcomes between the 2 groups ( P = 0.17 and P = 0.13, respectively). CONCLUSION: Considering potentially serious, sometimes lethal, adverse effects of antipsychotics, sedative antidepressants such as trazodone and mianserin may be a treatment option for delirium, especially in the elderly.

Antipsychotic treatment strategies for acute phase and treatment resistance in schizophrenia: A systematic review of the guidelines and algorithms.

BACKGROUND: To summarize the current state of knowledge on antipsychotic treatment strategies for the acute phase and treatment resistance in schizophrenia, we conducted a systematic review of guidelines and algorithms. METHODS: We conducted a systematic literature search to identify clinical guidelines and algorithms on this topic using MEDLINE and Embase. We extracted information on recommendations for antipsychotic treatment strategies, including those for non-response (i.e., increasing antipsychotic dose and switching to another antipsychotic) and treatment resistance. RESULTS: We identified a total of 17 guidelines/algorithms in various countries that were published after 2011. With respect to antipsychotic dose, most of the guidelines (N = 10/11) agreed starting with a low dose or the lowest licensed/effective dose and then titrating the dose upwards. Regarding antipsychotic treatment strategies for non-response, all of the guidelines (N = 9/9) recommended increasing antipsychotic dose towards the upper end of its approved dose range. Five guidelines suggested for increasing beyond the therapeutic dose range in exceptional cases, while overall 10 guidelines including them were negative about such strategy. The vast majority of guidelines (N = 16/17) recommended switching to another antipsychotic for non-response; however, some guidelines mentioned the lack of evidence for these strategies other than the use of clozapine. All the guidelines (N = 17/17) endorsed initiating clozapine after failure to respond to 2 different antipsychotics. Four guidelines endorsed an early use of clozapine, yet as the third antipsychotic. CONCLUSION: The currently available guidelines and algorithms recommended increasing antipsychotic dose and switching to another antipsychotic, particularly clozapine for treatment-resistant schizophrenia, during the acute phase of schizophrenia for non-response.

Single Versus Multiple Daily Dosing Regimens of Psychotropic Drugs for Psychiatric Disorders: A Systematic Review and Meta-Analysis.

OBJECTIVE: To compare efficacy and safety of single daily dosing (Single-DD) vs multiple daily dosing (Multiple-DD) regimens of psychotropic drugs, the authors conducted a systematic review and meta-analysis. DATA SOURCES: A systematic literature search of MEDLINE and Embase was conducted with keywords related to dosing regimens and psychotropic drugs (last search: December 30, 2019). STUDY SELECTION: Randomized controlled trials comparing clinical outcomes between Single-DD and Multiple-DD of the same formulation of the same psychotropic drugs in patients with psychiatric disorders were included. DATA EXTRACTION: Data on study discontinuation, psychopathology, and treatment-emergent adverse events (TEAEs) were extracted. RESULTS: A total of 32 studies with 34 paired comparisons involving 3,142 patients met the eligibility criteria and were included in the meta-analysis. Various types of psychotropic drugs were examined: antidepressants (22 comparisons), antipsychotics (7 comparisons), benzodiazepines (2 comparisons), mood stabilizers (2 comparisons), and antidepressant-benzodiazepine combination (1 comparison). There was no significant difference in study discontinuation due to all causes (30 comparisons, N = 2,883, risk ratio [RR] = 1.01, 95% CI = 0.94 to 1.09, P = .77), lack of efficacy (22 comparisons, N = 2,307, RR = 1.06, 95% CI = 0.84 to 1.33, P = .62), or adverse events (25 comparisons, N = 2,571, RR = 0.93, 95% CI = 0.75 to 1.14, P = .47) between the Single-DD and Multiple-DD groups. No significant difference was found in changes in psychopathology (8 comparisons, N = 1,337, standardized mean difference = 0.00, 95% CI = -0.11 to 0.11, P = .99) between the 2 groups. These results were also true for any type of psychotropic drugs. In terms of TEAEs, however, there were significant differences in anxiety (4 comparisons, N = 347, RR = 0.53, 95% CI = 0.33 to 0.84, P = .007) and sleepiness (3 comparisons, N = 934, RR = 0.82, 95% CI = 0.68 to 0.99, P = .04) in favor of the Single-DD group. CONCLUSIONS: The findings suggest Single-DD can be clinically adopted regardless of type of psychotropic drugs in patients with psychiatric disorders in general.

Antipsychotic treatment in the maintenance phase of schizophrenia: An updated systematic review of the guidelines and algorithms.

BACKGROUND: We updated our previous systematic review regarding clinical guidelines and algorithms on antipsychotic treatment in the maintenance phase of schizophrenia (doi: 10.1016/j.schres.2011.11.021) to incorporate and synthesize more recent findings to guide clinical practice. METHODS: We conducted a systematic literature search to identify clinical guidelines and algorithms describing antipsychotic treatment in the maintenance phase of schizophrenia using MEDLINE and Embase. We assessed overall quality of the guidelines/algorithms according to the AGREE II instrument and extracted information on treatment recommendations. RESULTS: We identified 20 guidelines/algorithms from various regions, including 11 updated or newly launched ones after the previous systematic review in 2012. All of the guidelines/algorithms satisfied a certain level of quality. Where mentioned, endorsements were sorted into "recommended", "partially recommended", or "not recommended". As for antipsychotic discontinuation strategy, a majority of guidelines/algorithms that mentioned this strategy did not recommend it for multiple-episode schizophrenia (N = 5/6). On the other hand, the guidelines/algorithms tended to shift from "not recommended" to "partially recommended" both for schizophrenia in general (N = 7/13, N = 7/8 for those published after 2013) and first-episode schizophrenia (N = 10/11, N = 7/7 for those published after 2013) regarding this strategy. All guidelines/algorithms (N = 9/9) converged to discourage antipsychotic intermittent/targeted strategy. Similar to antipsychotic discontinuation strategy, all of the updated or new guidelines/algorithms (N = 6/6) endorsed antipsychotic dose reduction/lower dose strategy. CONCLUSION: Recent clinical guidelines and algorithms on antipsychotic maintenance treatment in schizophrenia shifted more toward a possibility of antipsychotic discontinuation and dose reduction/lower dose strategies. Nonetheless, clinicians need to contemplate on the risk-benefit balance of these strategies for individual patients.