Drug Strategies and Treatment-Resistant Schizophrenia

Objectives: The aims of the paper are to review the notion of treatment resis- tance in schizophrenia and consider the factors important in determining non- responsiveness to standard neuroleptic treatment, and to review the strategies currently available in the treatment of such patients, including an evaluation of recently-introduced, novel drug treatments. Method: A selective review of the literature relating to treatment resistance was undertaken using medline searches, followed by cross-checking for further articles identified in these references. Results: The various treatment approaches available are considered, including adjunctive treatment with lithium or carbamazepine. The risks and benefits of high dose antipsychotic treatment are discussed. The possible benefits and side-effects of new treatments, particularly the atypical neuroleptics, are also reviewed. Conclusions: The reasons why a proportion of patients with schizophrenia fail to respond to standard neuroleptic treatment are ill-understood. Nevertheless, initial assessment should include identification of any factors that may be related to a patient's poor response, such as poor compliance, substance use or epilepsy. This may help to determine an appropriate treatment strategy. There is a need to be systematic and to ensure that patients be given an adequate trial of each treatment tested in terms of duration and dosage. The available evidence does not support the use of high doses of neuroleptics for the majority of patients. Adjunctive treatments, such as lithium, carbamazepine or benzodiazepines may be beneficial in non-responsive patients, particularly if certain target symptoms are present. Atypical neuroleptics, particularly clozapine, have proved particularly effective in non-responsive patients as well as those sensitive to the motor side-effects of standard drugs. However, the high risk of agranulocytosis with clozapine is a problem; also, the drug and the necessary haematological monitoring are expensive. There are hints that some of the other, new, atypical neuroleptics have some benefit in non-responsive patients, but controlled studies are required.

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Intramuscular maintenance treatment with ultra-high-dose long-acting injectable aripiprazole in an elderly patient suffering from chronic refractory schizophrenia: A case report

European Psychiatry ◽

10.1016/j.eurpsy.2016.01.2120 ◽

2016 ◽

Vol 33 (S1) ◽

pp. S573-S573 ◽

Cited By ~ 1

Author(s):

L. Bartova ◽

M. Dold ◽

N. Praschak-Rieder ◽

A. Naderi-Heiden ◽

S. Kasper

Keyword(s):

Side Effects ◽

Maintenance Treatment ◽

Rating Scale ◽

Antipsychotic Treatment ◽

High Dose ◽

Symptom Scale ◽

Meaningful Improvement ◽

Plasma Level Monitoring ◽

Competing Interest ◽

Long Acting

Long-acting injectable (LAI) aripiprazole is increasingly appreciated in the course of a maintenance treatment of schizophrenia due to efficacy in delaying – and decreasing relapse, and low rates of feared side effects. In line with the prescribing information, the maximal starting – as well as maintenance dose was restricted to 400 mg following a 26-day interval between the single doses.We present a 72-year-old female inpatient (66 kg) with an acute exacerbation of chronic refractory schizophrenia, exhibiting primarily positive symptoms including excessive persecutory delusions, self-care deficit, poor insight and insufficient adherence to continuous intake of oral medication. Since she developed a post-injection syndrome after an accidental intravascular administration of olanzapine LAI 405 mg, the antipsychotic treatment was switched to aripiprazole LAI 300 mg once monthly. Due to insufficient clinical response, aripiprazole LAI was gradually increased up to 1200 mg per month under continuous plasma level monitoring. Here, 2 single injections of aripiprazole LAI 300 mg were delivered into both gluteal muscles concurrently, every 14 days.Consequently, we observed a clinically meaningful improvement (a total-score reduction from 111 to 75 on the Positive and Negative Syndrome Scale), as well as no objectifiable side effects, assessed by “The Dosage Record Treatment Emergent Symptom Scale” and “The Barnes Akathisia Rating Scale”, despite multi-morbidity and rather advanced age of the patient.Our safe experience with applying the almost threefold higher monthly dose over 12 weeks may encourage researchers to further investigate the efficacy, tolerability as well as handling of highly dosed aripiprazole LAI in refractory schizophrenia.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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Sexual Dysfunction in Schizophrenia: A Narrative Review of the Mechanisms and Clinical Considerations

Psychiatry International ◽

10.3390/psychiatryint3010003 ◽

2021 ◽

Vol 3 (1) ◽

pp. 29-42

Author(s):

Amber N. Edinoff ◽

Catherine A. Nix ◽

Juliana M. Fort ◽

Jeanna Kimble ◽

Ryan Guedry ◽

...

Keyword(s):

Side Effects ◽

Sexual Dysfunction ◽

Structural Changes ◽

Treatment Resistance ◽

Thyroid Stimulating Hormone ◽

Serum Prolactin ◽

Antipsychotic Treatment ◽

High Prevalence ◽

Medication Side ◽

Specific Symptoms

Psychiatric disorders, in general, have a high prevalence of sexual problems, whether from the psychopathology of the disorder itself, pre-existing or co-morbid sexual disorder or from side effects of the treatment for mental disorders. Many patients report an already existing sexual dysfunction at the onset of diagnosis. The risk association for developing sexual dysfunction in patients with schizophrenia includes antipsychotic use and resulting hyperprolactinemia, age, gender, and disease severity. Medication side effects lead to nonadherence, and relapses lead to structural changes in the brain, treatment resistance, and worsening of symptoms. Findings in certain studies propose serum prolactin and thyroid-stimulating hormone measurement as a tool for assessing patients with schizophrenia for sexual dysfunction. Regarding specific symptoms, females especially reported decreased desire at baseline and galactorrhea after treatment. The findings of this review, therefore, suggest that sexual dysfunction may be present in patients with schizophrenia before starting antipsychotic treatment and that patients, especially those who are female, are likely to develop hyperprolactinemia with antipsychotic treatment. Aripiprazole may be an emergent treatment for sexual dysfunction in those who use antipsychotics. It is important for patients to consider sexual dysfunction prior to prescribing antipsychotics. Since sexual dysfunction can impact a patient’s quality of life and affect treatment adherence, it is important for physicians to be aware and monitor patients for symptoms.

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High dose antipsychotic treatment monitoring audit

BJPsych Open ◽

10.1192/bjo.2021.912 ◽

2021 ◽

Vol 7 (S1) ◽

pp. S348-S348

Author(s):

Jake Scott ◽

Jose Belda

Keyword(s):

Side Effects ◽

Physical Health ◽

Health Monitoring ◽

Clinical Benefit ◽

Health Assessment ◽

Antipsychotic Treatment ◽

High Dose ◽

Health Checks ◽

Increased Risk ◽

Multi Disciplinary Team

AimsTo quantify how many patients were prescribed high dose antipsychotic treatment (HDAT) and establish whether guidance for monitoring HDAT was being followed in an Assertive Outreach Team.BackgroundSevere mental health disorders are associated with significant premature mortality, predominantly due to physical health conditions. Antipsychotic medications are associated with side effects, including metabolic syndrome and QT prolongation, which increase the risk of serious physical illness. HDAT is defined as when the total dose of antipsychotics prescribed exceeds 100% of the maximum BNF dose, if each dose is expressed a percentage of its maximum dose. There is limited evidence of clinical benefit with HDAT but an increased risk of side effects. Patients prescribed HDAT should therefore be monitored for side effects and clinical benefit. Sussex Partnership NHS Foundation Trust developed a form specifically for this purpose, to be completed in addition to a physical health assessment.MethodAll patients on caseload were audited using the electronic notes. Current inpatients were excluded, as inpatient HDAT monitoring forms are attached to paper drug charts and therefore were not available for review.ResultA total of 61 patients were audited. Nine were excluded due to being inpatients. 16 were on community treatment orders and 26 were prescribed a long-acting antipsychotic injection. 10 were prescribed clozapine. The median number of medications prescribed was one. Four patients were prescribed HDAT ranging from 117-150% of the maximum BNF dose. Of these four, one had a HDAT form but this was out of date. 39 of 52 (75%) patients audited had had a physical health assessment in the past 12 months. Two of the 13 missing a physical health assessment were on HDAT.ConclusionPhysical health monitoring should be carried out for all patients on antipsychotics, but is particularly important for patients on HDAT. This audit identified a problem in both general physical health checks and HDAT monitoring. On discussion with the multi-disciplinary team a number of barriers to appropriate physical health monitoring were identified. There was a lack of awareness within the multi-disciplinary team that patients were receiving HDAT and regarding the implications for side effects. A reliable system to highlight the need for physical health checks was also missing and the team did not have sufficient equipment to perform the necessary checks. Identifying these barriers should enable improvements in physical health and HDAT monitoring which can be re-audited.

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Neuroleptic malignant syndrome: Case report and literature review

European Psychiatry ◽

10.1016/j.eurpsy.2017.01.822 ◽

2017 ◽

Vol 41 (S1) ◽

pp. S564-S564

Author(s):

R. Martín Gutierrez ◽

R. Medina Blanco ◽

P. Suarez Pinilla ◽

R. Landera Rodriguez ◽

M. Juncal Ruiz ◽

...

Keyword(s):

Literature Review ◽

Neuroleptic Malignant Syndrome ◽

Life Support ◽

Clinical Symptoms ◽

Altered Mental Status ◽

Antipsychotic Treatment ◽

High Dose ◽

Neuroleptic Treatment ◽

Pubmed Database ◽

Competing Interest

IntroductionNeuroleptic malignant syndrome (NMS) is an uncommon but potentially fatal adverse effect of neuroleptic, both classic and atypical drugs.ObjectiveTo review the incidence, clinical characteristics, diagnosis and treatment of NMS.AimWe have described the case of a man of 32 years of age diagnosed with bipolar disorder treated with lithium. He precised high-dose corticosteroids after having tonsillitis. Then, he presented manic decompensation requiring neuroleptic treatment (oral risperidone). After 72 hours, he presented an episode characterized by muscular rigidity, fever, altered mental status and autonomic dysfunction. Life support measures and suspension of neuroleptic treatment were required.MethodsA literature review of the NMS was performed using the PubMed database.ResultsThe frequency of NMS ranges from 0.02 to 2.4%. The pathophysiology is not clearly understood but the blockade of dopamine receptors seems to be the central mechanism. Some of the main risk factors described are: being a young adult, the concomitant use of lithium and metabolic causes, among others. NMS occurs most often during the first week of treatment or after increasing the dosage of the neuroleptic medication. Some issues of NMS are those related with diagnosis, treatment and reintroduction of antipsychotic treatment or not.ConclusionsNMS can be difficult to diagnose due to the variability in the clinical symptoms and presentation. Because of it diagnosis is of exclusion, clinicians should always take it into consideration when a patient is treating with neuroleptic, especially when the dosage has been recently increased. NMS is a clinical emergency.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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Maximizing response to first-line antipsychotics in schizophrenia

10.1093/med/9780198828761.003.0003 ◽

2018 ◽

Cited By ~ 1

Author(s):

Robert C. Smith ◽

Stefan Leucht ◽

John M. Davis

Keyword(s):

Side Effects ◽

Negative Symptoms ◽

Antidepressant Drug ◽

Adjunctive Treatment ◽

Antipsychotic Treatment ◽

Inadequate Response ◽

First Line ◽

Adequate Dose ◽

Efficacy Outcome ◽

Meta Analyses

The choice of first-line antipsychotic treatment for patients with schizophrenia should balance considerations of differential efficacy of antipsychotics against the relative risk of different side effects. In terms of efficacy, recent meta-analyses have shown that antipsychotics are not equivalent in efficacy. Clozapine, amisulpride, olanzapine, and risperidone show small to moderate, but statistically significant, differences, indicating greater efficacy compared to a number of other antipsychotics on some primary efficacy outcome measures. Amisulpride and cariprazine have the strongest evidence for greater efficacy for treating negative symptoms relative to other antipsychotics. In terms of side effects, clozapine and olanzapine have among the highest weight gain potential and amisulpride has more effects on QTc prolongation and prolactin elevation than other commonly used antipsychotics. Adjunctive treatment with an antidepressant drug may improve response in patients with schizophrenia who also have severe depressive or negative symptoms. For a patient with an inadequate response to an adequate dose and duration of the initial antipsychotic choice, switching to another antipsychotic with a different receptor profile may improve response, although evidence is limited. There is little evidence to support using doses above the therapeutic range other than in exceptional circumstances.

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Trends of Anticholinergics and Antipsychotics Prescribing at Chainama Hills College Hospital, Lusaka-Zambia

Journal of Preventive and Rehabilitative Medicine ◽

10.21617/jprm2021.327 ◽

2021 ◽

Vol 3 (2) ◽

pp. 24-31

Author(s):

Francisca T Bwalya ◽

◽

James Mwanza ◽

Paul Ravi ◽

◽

...

Keyword(s):

Side Effects ◽

Atypical Antipsychotic ◽

Treatment Guidelines ◽

Anticholinergic Drug ◽

Antipsychotic Treatment ◽

High Dose ◽

Anticholinergic Drugs ◽

Typical Antipsychotic ◽

Extrapyramidal Side Effects ◽

College Hospital

Introduction:Antipsychotics are the main pharmacological treatment for psychosis. Anticholinergic drugs are sometimes prescribed with antipsychotics to treat or as prophylaxis for extrapyramidal side effects. Antipsychotic treatment guidelines recommend that anticholinergics should not be prescribed indiscriminately as prophylaxis for extrapyramidal side effects to patients using antipsychotic drugs, but only when there is high risk or evidence of extrapyramidal side effects, as they can cause significant central and peripheral side effects which have a potential to affect treatment outcomes. The objective of the study was to assess the trends in the prescribing of antipsychotics and anticholinergics.Methods:A cross sectional study was conducted at Chainama Hills College Hospital in Zambia. An open-ended questionnaire was administered to 26 prescribers and 311 files for patients were reviewed who had an antipsychotic or anticholinergic drug prescribed. The prescription pattern of patient files was compared with theNational Institute for Health and Care Excellenceguidelines as a gold standard.Results:The antipsychotic distribution showed that 76.1% were prescribed a typical antipsychotic, 18.1% an atypical antipsychotic and 5.8% were on both typical and atypical antipsychotic. 28.2% of the patients on antipsychotics were prescribed anticholinergics (Trihexyphenidyl). 46.2% of the prescribing clinicians stated that they prescribe anticholinergics when a patient develops extrapyramidal side effects rather than concurrently with antipsychotics or when a high dose of antipsychotics has been prescribed.Conclusion:The trend in antipsychotic and anticholinergic prescribing in Lusaka-Zambia were not consistent with recommended guidelines. Majority of patients are on typical antipsychotics rather than atypical antipsychotics. Most patients were administered above optimal dose of antipsychotics though polypharmacy was solemnly practiced. Recommend that further studies to explore factors contributing to this trend are conducted.

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Efficacy and safety of oral dapsone in acne vulgaris – experience of a tertiary care teaching hospital in central Lahore

Journal of Fatima Jinnah Medical University ◽

10.37018/xqbw1463 ◽

2020 ◽

Vol 14 (2) ◽

pp. 87-90

Author(s):

Sadaf Amin Chaudhry ◽

Nadia Ali Zafar ◽

Rabia Hayat ◽

Ayesha Noreen ◽

Gulnaz Ali ◽

...

Keyword(s):

Side Effects ◽

Therapeutic Option ◽

Acne Vulgaris ◽

Treatment Options ◽

Tertiary Care ◽

Poor Response ◽

Global Assessment Scale ◽

Severe Acne ◽

Hematologic Profile

Background: Acne is the eighth most prevalent disease affecting 9.4% of the population worldwide and its prevalence in our country is estimated to be around 5%. Severe inflammatory acne is most likely to leave scars and in order to prevent facial disfigurement due to acne scarring, early treatment is desirable. Various treatment options have been formulated for acne, and are tailored according to the severity of the disease. Numerous clinical trials have been conducted till now, to determine the usefulness and side effect profile of such therapies, making acne treatment a highly studied area in dermatology. Objective of this study is to highlight the fact that oral Dapsone could be used as a cheaper alternate to isotretinoin in recalcitrant severe acne, especially in females where retinoids are sometimes contraindicated. Patients and methods: 51 patients, suffering from severe nodulocystic acne, fulfilling the criteria, were enrolled from the Department of Dermatology, Sir Ganga Ram Hospital, Lahore. All the study patients were given oral Dapsone 50mg for initial two weeks and then 100mg daily for the next 10 weeks along with oral cimetidine and topical clindamycin application twice daily. Investigator Global Assessment Scale (IGAS) was employed to measure effectiveness. The treatment was considered ʽeffectiveʹ if the patient achieves 2 or more than 2-grade improvement or almost clear or clear skin at the end of 12 weeks according to IGAS scale. The lesion counts were also done before the start of therapy (day 1) and at every two weeks follow up for 12 weeks. The change in lesion count observed between the baseline number and that seen at follow up visits was also used to evaluate the effectiveness of oral Dapsone. Safety was analyzed by fortnightly visits of the patients to look for any undesirable side effects and monitoring of the hematologic profile of the patients. Final follow up was done at the end of 16 weeks. Results: The study was conducted on 51 patients, with a ratio of 1:3 for males and females and a mean age of 25.2 years (SD ±5.81). At 12th week, patients had significant reduction in their acne lesions; with 7 patients (13.7%) showing completely clear skin, 17 patients (33.3%) had almost clear skin, 5 patients (9.8%) had 3-grade improvement. Twelve patients (23.5%) had 2-grade improvement from baseline score and only 2 patients (3.9%) had 1-grade improvement from baseline. Based on percentage reduction of lesions, excellent response was seen in 32 patients (62.7%), good response in 9 patients (17.6%), moderate response in 2 patients (3.9%), while no patient showed poor response. Dapsone was discontinued in 8 patients due to derangement of hematologic profile. Conclusion: Oral Dapsone, when given carefully, is a very effective therapeutic option in severe recalcitrant acne, with limited side effects.

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Quality-by-Design Enabled Chitosan Nanoparticles for Antitubercular Therapy: Formulation, Statistical Optimization, and In vitro Characterization

Current Drug Therapy ◽

10.2174/1574885515666200722150305 ◽

2020 ◽

Vol 15 ◽

Author(s):

Manasi M. Chogale ◽

Sujay S. Gaikwad ◽

Savita P. Kulkarni ◽

Vandana B. Patravale

Keyword(s):

Side Effects ◽

Treatment Regimen ◽

Research Work ◽

Chitosan Nanoparticles ◽

In Vitro Release ◽

Antitubercular Therapy ◽

Prolonged Treatment ◽

High Dose ◽

Average Size

Background: Tuberculosis (TB) continues to be among the leading causes for high mortality among developing countries. Though a seemingly effective treatment regimen against TB is in place, there has been no significant improvement in the therapeutic rates. This is primarily owing to the high drug doses, their associated sideeffects, and prolonged treatment regimen. Discontinuation of therapy due to the severe side effects of the drugs results in the progression of the infection to the more severe drug-resistant TB. Objectives: Reformulation of the current existing anti TB drugs into more efficient dosage forms could be an ideal way out. Nanoformulations have been known to mitigate the side effects of toxic, high-dose drugs. Hence, the current research work involves the formulation of Isoniazid (INH; a first-line anti TB molecule) loaded chitosan nanoparticles for pulmonary administration. Methods: INH loaded chitosan nanoparticles were prepared by ionic gelation method using an anionic crosslinker. Drugexcipient compatibility was evaluated using DSC and FT-IR. The formulation was optimized on the principles of Qualityby-Design using a full factorial design. Results: The obtained nanoparticles were spherical in shape having an average size of 620±10.97 nm and zeta potential +16.87±0.79 mV. Solid state characterization revealed partial encapsulation and amorphization of INH into the nanoparticulate system. In vitro release study confirmed an extended release of INH from the system. In vitro cell line based safety and efficacy studies revealed satisfactory results. Conclusion: The developed nanosystem is thus an efficient approach for antitubercular therapy.

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TNF-Alpha Inhibitors for Chronic Urticaria: Experience in 20 Patients

Journal of Allergy ◽

10.1155/2013/130905 ◽

2013 ◽

Vol 2013 ◽

pp. 1-4 ◽

Cited By ~ 13

Author(s):

Freja Lærke Sand ◽

Simon Francis Thomsen

Keyword(s):

Side Effects ◽

Chronic Urticaria ◽

Treatment Options ◽

Significant Proportion ◽

Response Duration ◽

Immunosuppressive Drugs ◽

Tnf Alpha ◽

High Dose ◽

Duration Of Treatment ◽

Durable Response

Patients with severe chronic urticaria may not respond to antihistamines, and other systemic treatment options may either be ineffective or associated with unacceptable side effects. We present data on efficacy and safety of adalimumab and etanercept in 20 adult patients with chronic urticaria. Twelve (60%) patients obtained complete or almost complete resolution of urticaria after onset of therapy with either adalimumab or etanercept. Further three patients (15%) experienced partial response. Duration of treatment ranged between 2 and 39 months. Those responding completely or almost completely had a durable response with a mean of 11 months. Six patients (30%) experienced side effects and five patients had mild recurrent upper respiratory infections, whereas one patient experienced severe CNS toxicity that could be related to treatment with TNF-alpha inhibitor. Adalimumab and etanercept may be effective and relatively safe treatment options in a significant proportion of patients with chronic urticaria who do not respond sufficiently to high-dose antihistamines or in whom standard immunosuppressive drugs are ineffective or associated with unacceptable side effects.

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Bilateral dysthyroid compressive optic neuropathy responsive to teprotumumab

European Journal of Ophthalmology ◽

10.1177/1120672121991042 ◽

2021 ◽

pp. 112067212199104

Author(s):

Catherine J Hwang ◽

Erin E Nichols ◽

Brian H Chon ◽

Julian D Perry

Keyword(s):

Side Effects ◽

Optic Neuropathy ◽

Surgical Decompression ◽

Thyroid Eye Disease ◽

Eye Disease ◽

High Dose ◽

Compressive Optic Neuropathy ◽

Traditional Management ◽

Immune Mediated ◽

Orbital Radiation

Thyroid eye disease is an auto-immune mediated orbitopathy which can cause dysthyroid compressive optic neuropathy. Traditional management of active thyroid eye disease includes temporizing high-dose steroids, orbital radiation and surgical decompression, which each possess significant limitations and/or side effects. Teprotumumab is an IGF-IR inhibitor recently FDA-approved for active thyroid eye disease. The authors report reversal of bilateral dysthyroid compressive optic neuropathy managed medically utilizing teprotumumab.

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