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For patients with major depressive disorder (MDD) experiencing side-effects or non-response to their first antidepressant, little is known regarding the effect of switching between a tricyclic antidepressant (TCA) and a selective serotonin reuptake inhibitor (SSRI).
To compare the switch between the TCA nortriptyline and the SSRI escitalopram.
Among 811 adults with MDD treated with nortriptyline or escitalopram for up to 12 weeks, 108 individuals switched from nortriptyline to escitalopram or vice versa because of side-effects or non-response (trial registration: EudraCT No.2004-001723-38 (https://eudract.ema.europa.eu/) and ISRCTN No.03693000 (http://www.controlled-trials.com)). Patients were followed for up to 26 weeks after switching and response was measured with the Montgomery–Åsberg Depression Rating scale (MADRS). We performed adjusted mixed-effects linear regression models with full information maximum likelihood estimation reporting β-coefficients with 95% CIs.
Switching antidepressants resulted in a significant decrease in MADRS scores. This was present for switchers from escitalopram to nortriptyline (n = 36, β = −0.38, 95% CI −0.51 to −0.25, P<0.001) and from nortriptyline to escitalopram (n = 72, β = −0.34, 95% CI −0.41 to −0.26, P<0.001). Both switching options resulted in significant improvement among individuals who switched because of non-response or side-effects. The results were supported by analyses on other rating scales and symptom dimensions.
These results suggest that switching from a TCA to an SSRI or vice versa after non-response or side-effects to the first antidepressant may be a viable approach to achieve response among patients with MDD.
Declarations of interest
K.J.A. holds an Alberta Centennial Addiction and Mental Health Research Chair, funded by the Government of Alberta. K.J.A. has been a member of various advisory boards, received consultancy fees and honoraria, and has received research grants from various companies including Johnson and Johnson Pharmaceuticals Research and Development and Bristol-Myers Squibb Pharmaceuticals Limited. D.S. has served on advisory boards for, and received unrestricted grants from, Lundbeck and AstraZeneca. A.F. and P.M. have received honoraria for participating in expert panels for Lundbeck and GlaxoSmithKline.
Few studies have looked at subjective memory impairment from electroconvulsive therapy (ECT) after treatment completion. We aimed to systematically review all available evidence for subjective post-treatment effects.
We included 16 studies in this review. There was considerable between-study heterogeneity in clinical population, ECT modality and assessment scales used. The most common assessment scale (eight studies) was the Squire Subjective Memory Questionnaire. The majority of studies reported an improvement in subjective memory after ECT, which correlated with improved depression scores. Subjective complaints were fewer in studies that used ultra-brief pulse ECT. Longer pulse widths were associated with more subjective complaints, as was female gender and younger age of treatment in the largest study.
There is considerable heterogeneity between studies, limiting meaningful conclusions. Ultra-brief pulse ECT appears to result in fewer subjective complaints.
This study examined factors influencing parent willingness to use D-Cycloserine (DCS) for treating child anxiety. N = 222 parents were given information about using DCS to treat anxiety. They were then asked to rate their willingness to allow their child to take DCS/antibiotics for mild anxiety, severe anxiety, or an infection. The associations between willingness to use DCS and parental trait anxiety, demographics, as well as specific concerns regarding the medication, were examined. Parents could also provide written responses regarding their attitudes to DCS, which were analysed for themes. Parents reported concerns regarding potential side-effects from DCS. More severe anxiety was associated with more willingness to consent; however, parents were more willing to use antibiotics to treat an infection than DCS to treat their child's anxiety. The degree of perceived benefit from DCS was most strongly associated with parents’ willingness to use it. Overall, parents expressed mixed views, reporting they would consider using DCS to treat their child; however, they had significant concerns about it. Results suggest providing parents with information explaining how DCS works, its risks and potential benefits may increase its acceptability.
During the 1970s there was a gross loss of public confidence in infant diphtheria-tetanus-pertussis (DTP) vaccination in the UK. As well as febrile reactions and convulsions, permanent neurological damage was ascribed to the pertussis component of the vaccine, and those concerns resonated worldwide. The subsequent recognition of human herpes virus 6 (HHV-6) and 7 (HHV-7) as common sources of fever in infancy suggests that they were the main underlying cause of what was reported as DTP constitutional side-effects. With more precise data on the incidence of HHV-6/7 and other virus infections in early life it would be possible to model the concurrence of viral illnesses with routine immunizations. Adventitious viral infections may be the cause of side-effects ascribed to the numerous childhood immunizations now being given.
Cortical hyperostosis is a very uncommon side-effect of prolonged prostaglandin therapy with distinctive radiological signs that may be accompanied by painful swelling of the limbs and responds rapidly to withdrawal of therapy.
The belief bias effect is a phenomenon which occurs when we think that we judge an argument based on our reasoning, but are actually influenced by our beliefs and prior knowledge. Evans, Barston and Pollard carried out a psychological syllogistic reasoning task to prove this effect. Participants were asked whether they would accept or reject a given syllogism. We discuss one specific case which is commonly assumed to be believable but which is actually not logically valid. By introducing abnormalities, abduction and background knowledge, we adequately model this case under the weak completion semantics. Our formalization reveals new questions about possible extensions in abductive reasoning. For instance, observations and their explanations might include some relevant prior abductive contextual information concerning some side-effect or leading to a contestable or refutable side-effect. A weaker notion indicates the support of some relevant consequences by a prior abductive context. Yet another definition describes jointly supported relevant consequences, which captures the idea of two observations containing mutually supportive side-effects. Though motivated with and exemplified by the running psychology application, the various new general abductive context definitions are introduced here and given a declarative semantics for the first time, and have a much wider scope of application. Inspection points, a concept introduced by Pereira and Pinto, allows us to express these definitions syntactically and intertwine them into an operational semantics.
Objectives: To study the frequency of use, indications and reported side-effects of antidepressants in the treatment of adult inpatients at a UK secure hospital.
Methods: Cross-sectional survey of the use of antidepressants for forensic rehabilitation patients, together with structured interviews with the treating psychiatrists.
Results: A total of 94 patients (40.7%) were prescribed antidepressants. The majority (68.9%) were prescribed SSRIs. Antidepressant usage was associated with female gender, depression and emotionally unstable personality disorder. Patients with learning disabilities and pervasive developmental disorders were less likely to be prescribed antidepressants than the rest. Only 10 patients (10.6%) had a formal diagnosis of depression, anxiety or obsessive compulsive disorder. For 67.0% of patients the plan was to continue with the antidepressant long-term. Although 83.0% of psychiatrists said they had asked about side-effects, few (14.9%) had asked about sexual side-effects and only 3.2% of patients were reported as having side-effects.
Conclusions: Long-term antidepressant usage in this population was common. The reported incidence of side-effects was very low and is likely to be much higher in reality. Psychiatrists should make regular inquiry about side-effects, including sexual side-effects when appropriate, as well as regularly reviewing the need for continuing treatment.
Understanding individual differences in susceptibility to antidepressant therapy side-effects is essential to optimize the treatment of depression.
We performed genome-wide association studies (GWAS) to search for genetic variation affecting the susceptibility to side-effects. The analysis sample consisted of 1439 depression patients, successfully genotyped for 421K single nucleotide polymorphisms (SNPs), from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. Outcomes included four indicators of side-effects: general side-effect burden, sexual side-effects, dizziness and vision/hearing-related side-effects. Our criterion for genome-wide significance was a prespecified threshold ensuring that, on average, only 10% of the significant findings are false discoveries.
Thirty-four SNPs satisfied this criterion. The top finding indicated that 10 SNPs in SACM1L mediated the effects of bupropion on sexual side-effects (p=4.98×10−7, q=0.023). Suggestive findings were also found for SNPs in MAGI2, DTWD1, WDFY4 and CHL1.
Although our findings require replication and functional validation, this study demonstrates the potential of GWAS to discover genes and pathways that could mediate adverse effects of antidepressant medication.
Background: Adherence to treatment is a complex and poorly understood phenomenon. This study investigates the relationship between older depressed patients’ adherence to antidepressants and their beliefs about and knowledge of the medication.
Methods: Assessment was undertaken of 108 outpatients over the age of 55 years diagnosed with depressive disorder and treated for at least four weeks with antidepressants. Adherence was assessed using two self-report measures: the Medication Adherence Rating Scale (MARS) and a Global Adherence Measure (GAM). Potential predictors of adherence investigated included sociodemographic, medication and illness variables. In addition, 33 carers were interviewed regarding general medication beliefs.
Results: 56% of patients reported 80% or higher adherence on the GAM. Sociodemographic variables were not associated with adherence on the MARS. Specific beliefs about medicines, such as “my health depends on antidepressants” (necessity) and being less worried about becoming dependant on antidepressants (concern) were highly correlated with adherence. General beliefs about medicines causing harm or being overprescribed, experiencing medication side-effects and severity of depression also correlated with poor adherence. Linear regression with the MARS as the dependent variable explained 44.3% of the variance and showed adherence to be higher in subjects with healthy specific beliefs who received more information about antidepressants and worse with depression severity and autonomic side-effects.
Conclusions: Our findings strongly support a role for specific beliefs about medicines in adherence. Challenging patients’ beliefs, providing information about treatment and discussing side-effects could improve adherence. Poor response to treatment and medication side-effects can indicate poor adherence and should be considered before switching medications.
To quantify factors influencing iron supplementation compliance and
haemoglobin (Hb) concentrations among pregnant women participating in an
iron supplementation programme under routine field conditions.
Cross-sectional interviews and Hb measurements.
Albay and Sorsogon provinces, Bicol, Philippines.
Three hundred and forty-six pregnant women receiving iron supplements via the
Philippine iron supplementation programme.
Women had a mean Hb concentration of 10.75 ± 1.43 g
dl−1, and 56.4% were anaemic (Hb < 11.0
g dl−1). On average, the first prenatal visit occurred
at nearly 4 months (3.80 ± 1.56). The ratio of visits to number
of months pregnant was 0.51 ± 0.24. Self-reported consumption of
pills received was 85% (0.85 ± 0.23), although pill counts
suggested that consumption was 70% (0.70 ± 0.35). Using multiple
regression, an earlier first prenatal visit and greater self-reported
compliance were positively associated with Hb concentrations. Additionally,
perceived health benefits from taking the supplements and higher health
programme knowledge were positively associated with pill consumption, while
experiencing side-effects and disliking the taste of the supplements were
associated with lower pill consumption. A greater number of living children
was negatively associated with the frequency of prenatal visits. The number
of children was also directly negatively associated with Hb
Compliance was positively related to Hb concentrations. Several factors
associated with greater compliance were identified, including marital
status, number of children, health programme knowledge, side-effects,
perceived health benefits, and dislike of taste. Some of these factors may
serve as avenues for interventions to increase compliance, and ultimately Hb
In this chapter, the main aspects of HIV in the adult population and its effects on mental state are considered in terms of epidemiology, clinical manifestations and management. The psychiatric management of individuals with HIV and AIDS may be complicated by biological manifestations of infections which may contribute to altered behaviour. The mainstay of treatment of HIV/AIDS is with antiviral agents of three broad classes, nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors and protease inhibitors. The chapter lists out reported psychiatric side-effects of antiretroviral medications used in the treatment of HIV/AIDS. HIV and AIDS affect individuals, families, friends and the wider community in general. Hence the inclusion of social support is an essential adjunct to successful treatment of any HIV-associated psychiatric mortality. However, the appearance of resistance to antiretroviral medications may eventually result in increases in the prevalence of HIV and AIDS.
Objectives: To examine the knowledge and experiences of side-effects and their monitoring in patients prescribed atypical antipsychotic medications.
Methods: A tick box survey was designed to ask questions of patients prescribed atypical antipsychotic medications about side-effects and monitoring for them. This survey was distributed anonymously to all suitable outpatient attendees over a three month period who had been prescribed atypical antipsychotic medication for at least one year.
Results: Seventy-four of the 90 surveys (82%) distributed were returned complete. Fifty-six (76%) of those surveyed said they were currently experiencing side-effects. Twenty-two (39%) said they had not told their psychiatrist about the side-effects. Weight gain was most commonly complained of (49%). Forty-five (61%) said that they had had no monitoring blood tests in the past year. Fifty-one (69%) did not know that certain monitoring blood tests were recommended.
Conclusions: Patients prescribed atypical antipsychotic medications are not currently being monitored as best practice dictates. It cannot be assumed that GPs will pursue this monitoring. More resources are needed for mental health services so that adequate monitoring services can be provided.
Mental health nurses are relative latecomers to nurse prescribing. This is primarily because nurse prescribing has been seen as more appropriate for general nurses, particularly those working in the community or primary care. Pharmacists and psychiatrists were concerned about the complexity of prescribing for clients with mental health problems and felt that the training of mental health nurses and their clinical experience did not fit them to take on a prescribing role. These, and other impressions, may have influenced which groups of nurses were first selected to become nurse prescribers. However, recent studies have indicated that mental health nurses add considerably to the effectiveness of assessments and care plans, and that they are in an ideal position to integrate drug treatments with a wide range of non-pharmacological therapies knowledgeably, safely, effectively and in a manner that is acceptable to the patient. They have also been found to have an important role to play in monitoring the side effects of drugs and in providing education about medication, and in maintaining a therapeutic alliance with clients on long-term drug treatment. Whatever the limitations, mental health nurses as prescribers may still be deemed to have by some professional groups, and even by themselves, at this stage in the evolution of nurse prescribing, it is now inevitable that they will play a significant part in the overall improvement of mental health services during this decade. They are likely to challenge the existing prescribing practices and help in identifying the conditions under which medication is most therapeutic.
This study examined the spectrum of subjective experiences which patients attribute to the use of antipsychotic medication.
We collected interview data and answers to structured questions based on a comprehensive checklist in 77 patients using various types of classical or atypical antipsychotic drugs.
The responses of the patients could be categorized into psychological and somatic domains. The psychological domain could be subdivided into emotional, cognitive and sociability domains. The somatic set could be subdivided into activation and physiological domains.
Our data reveal that the same effects may be experienced in either a positive or a negative way by different patients. We conclude that existing scales for measuring subjective effects of antipsychotic medication are incomplete.
This paper provides an overview of the effects of in vitro fertilization
(IVF) on the children born from it. One of the main problems with IVF to date
remains the high incidence of multiple pregnancies, which carry an inherent
higher risk of preterm delivery and, therefore, of increased morbidity and
mortality in newborns. Further, singleton pregnancies and twin pregnancies
from IVF compared to control singleton or twin pregnancies appear to be at
higher risk of preterm birth and low birth weight. Whether this is an effect
of the procedure per se or is related to maternal factors, or a combination of
both, remains to be studied. The risk of congenital malformations does not,
with the available data, seem to be elevated. As of now, it remains unclear
whether embryo freezing is a safe procedure. Psychomotor development of
children born through IVF does not seem to be disturbed. Until further and
more extensive studies are conducted, it remains unclear whether IVF poses
long-term risks for the children.
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