[Intensive exposure treatment for obsessive compulsive disorder in old age.] / Intensieve exposure bij obsessieve-compulsieve stoornis op oudere leeftijd.

The absence of treatment studies for obsessive compulsive disorder (OCD) in older adults and the fact that OCD typically starts at a young age and often follows a chronic, fluctuating course quickly leads to therapeutic nihilism for older adults with OCD. In this case report, we present a 72-year-old man with OCD symptoms from the age of 35, who has only been treated with medication and psychotherapy for a recurrent depressive disorder. After a short, intensive exposure and response prevention treatment (four days in two weeks), the OCD symptoms and the depressive symptoms were fully in remission and all medications (venlafaxine, olanzapine, depakine) were discontinued. Treatment gains were maintained with persistent remission until 18 months follow up. This case report shows that a comorbid depressive disorder may lead to undertreatment of OCD. It also shows that long standing OCD can be successfully treated in older adults.

Impaired action-safety learning and excessive relief during avoidance in patients with anxiety disorders.

Anxiety-related disorders are characterized by high levels of avoidance, but experimental research into avoidance learning in patients is scarce. To fill this gap, we compared healthy controls (HC, n = 47) with patients with obsessive-compulsive disorder (OCD, n = 33), panic disorder with agoraphobia (PDA, n = 40), and post-traumatic stress disorder (PTSD, n = 66) in a computer-based avoidance learning task, in order to examine (1) differences in rates of avoidance responses, (2) differences in action-safety learning during avoidance, and (3) differences in subjective relief following successful avoidance. The task comprised aversive negative pictures (unconditional stimulus, US) that followed pictures of two colored lamps (conditional stimuli, CS+), but not a third colored lamp (safety stimulus, CS-), and could be avoided by pressing a button during one CS+ (CS+ avoidable) but not the other (CS+ unavoidable). Participants rated their US-expectancy and level of relief on a trial-by-trial basis. Compared to the HC group, patient groups displayed higher levels of avoidance to the safety stimulus, and higher levels of US-expectancy and relief following the safety and avoidable danger stimulus. We propose that patients with anxiety disorders have low confidence in the safety consequences of avoidance actions, which induces increased relief during US omissions that reinforce the avoidance action.

The impact of a history of child abuse on cognitive performance: a cross-sectional study in older patients with a depressive, anxiety, or somatic symptom disorder.

BACKGROUND: Child abuse is a major global burden with an enduring negative impact on mental and physical health. A history of child abuse is consistently associated with worse cognitive performance among adults; data in older age groups are inconclusive. Since affective symptoms and cognitive functioning are interrelated among older persons, a synergistic effect can be assumed in patients with affective symptoms who also have suffered from child abuse. This study examines the association between a history of child abuse and cognitive performance in such patients. METHODS: Cross-sectional data were collected from the 'Routine Outcome Monitoring for Geriatric Psychiatry & Science' project, including 179 older adults (age 60-88 years) with either a unipolar depressive, any anxiety, or somatic symptom disorder referred to specialized geriatric mental health care. A history of physical, sexual, and psychological abuse, and emotional neglect was assessed with a structured interview. Cognitive functioning was measured with three paper and pencils tests (10-words verbal memory test, Stroop Colour-Word test, Digit Span) and four tests from the computerized Cogstate Test Battery (Detection Test, Identification Test, One Card Learning Test, One Back Test). The association between a history of child abuse and cognitive performance was examined by multiple linear regression analyses adjusted for covariates. RESULTS: Principal component analyses of nine cognitive parameters revealed four cognitive domains, i.e., visual-verbal memory, psychomotor speed, working memory and interference control. A history of child abuse was not associated with any of these cognitive domains. However, when looking at the specific types of child abuse separately, a history of physical abuse and emotional neglect were associated with poorer interference control. A history of physical abuse was additionally associated with better visual-verbal memory. CONCLUSIONS: The association between a history of child abuse and cognitive performance differs between the different types of abuse. A history of physical abuse might particularly be a key determinant of cognitive performance in older adults with a depressive, anxiety, or somatic symptom disorder. Future studies on the impact of these disorders on the onset of dementia should take child abuse into account. TRIAL REGISTRATION: ROM-GPS is registered at the Dutch Trial Register ( NL6704 at www.trialregister.nl ).

Comorbid depression and treatment of anxiety disorders, OCD, and PTSD: Diagnosis versus severity.

BACKGROUND: Although anxiety and depression are highly comorbid disorders, it remains unclear whether and how a concurrent depression affects the outcome of anxiety treatment. METHOD: Using anonymized routine outcome monitoring (ROM) data of 740 patients having received specialized treatment for an anxiety disorder, OCD, or PTSD, this study investigates whether a comorbid diagnosis of depression and/or self-reported depression severity levels relate to the patients' improvement following anxiety treatment. RESULTS: The results show that both the patients with and those without comorbid depression had profited similarly from the anxiety, OCD, or PTSD treatment, regardless of whether depression was merely diagnosed prior to treatment or based on self-reported severity (and assuming a smallest effect size of interest of d = 0.35/r = .2). Importantly, the post-treatment reductions in self-reported depressive symptoms were strongly and positively related to the reductions in self-reported anxiety symptoms and disorder-related disability. LIMITATIONS: Causal inferences cannot be made due to the retrospective cross-sectional design. CONCLUSIONS: The outcomes obtained in a naturalistic patient sample support current treatment guidelines recommending evidence-based treatment for anxiety disorders, OCD, and PTSD in patients with and without a comorbid depression. Future treatment studies are recommended for investigate the (bi)directionality of anxiety and depressive symptoms throughout treatment.

Impact of childhood trauma on multidimensional frailty in older patients with a unipolar depressive-, anxiety- or somatic symptom disorder.

OBJECTIVES: Frailty marks an increased risk for adverse health outcomes. Since childhood trauma is associated with the onset of physical and mental health diseases during the lifespan, we examined the link between childhood trauma and multidimensional frailty. METHOD: A cross-sectional study embedded in a clinical cohort study (ROM-GPS) of older (≥60 years) patients (n=182) with a unipolar depressive-, anxiety- and/or somatic symptom disorder according to DSM-criteria referred to specialized geriatric mental health care. Frailty was assessed with the Tilburg Frailty Indicator (TFI), comprising a physical, psychological, and social dimension. Physical, sexual and psychological abuse and emotional neglect before the age of 16 years was measured with a structured interview. RESULTS: Of 182 patients, 103 (56.6%) had experienced any childhood trauma and 154 (84.6%) were frail (TFI sum score ≥5). Linear regression analyses, adjusted for lifestyle, psychological and physical-health factors, showed that the presence of any type of childhood trauma was not associated with the TFI sum score, however when considered separately, physical abuse was (ß=0.16, p=.037). Regarding the specific frailty dimensions, any childhood trauma was associated with social frailty (ß=0.18, p=.019), with emotional neglect as main contributor. CONCLUSION: These findings demonstrate a complex link between different types of childhood trauma and multidimensional frailty among older psychiatric patients. Regarding the three dimensions of frailty, social frailty seems most affected by childhood trauma. This may have been underestimated until now and should receive more attention in clinical care and future research.

[Decrease of depression and outcome in treatment of anxiety disorders - an observational study of ROM data]. / Afname van depressie en de uitkomst bij de behandeling van angststoornis ­ een observationele studie van ROM-data.

BACKGROUND: Most mental health hospitals in the Netherlands use disorder specific standards of care. In case of comorbidity, we lack evidence in choosing the treatment of preference when both depressive- and anxiety disorder(s) are present in the same patient.
AIM: To investigate the prevalence of depression and anxiety (including obsessive compulsive disorder and post-traumatic stress disorder) in an outpatient mental health hospital population treated for their anxiety disorder, and to investigate the difference in outcome of (anxiety) treatment between patients with and without a comorbid depressive disorder.
METHOD: A retrospective study using outcome data from 2012 to 2017. In this period, we identified 127 patients for whom outcome data and diagnostic criteria were available. Comorbidity in this group was determined by a clinical interview. During treatment symptoms were monitored using self-reporting scales, among others the Inventory of Depressive Symptomatology (IDS) and the Beck Anxiety Inventory (BAI).
RESULTS: In 46,5% of the patients a comorbid depressive disorder was diagnosed. No significant difference in treatment outcome was observed between the group of patients with and the group of patients without a comorbid depressive disorder. However, the amount of reduction of depressive symptoms measured by the ids was a good predictor of the reduction of anxiety: a faster reduction of depressive symptoms predicts a better outcome of the treatment of anxiety.
CONCLUSION: Comorbid depressive disorders were observed in almost half of the patients treated in specialized (outpatient) clinics for anxiety disorders. A slower reduction of depressive symptoms predicts worse outcome of the treatment of anxiety.

[Intensive, short-term treatment for adolescents with persevering obsessive-compulsive disorder: three case-reports]. / Intensieve kortdurende behandeling voor jongeren met een hardnekkige obsessieve-compulsieve stoornis: drie gevalsbeschrijvingen.

Approximately 40% of adolescents with obsessive-compulsive disorder (ocd) do not improve sufficiently from standard cognitive behavioral therapy, and are at risk for a chronic course of the symptomatology as well as stagnation in their development. There has hardly been any research into next step evidence-based treatments for adolescents with persevering ocd. We treated three adolescents with persevering ocd with an eight-day intensive, therapist-assisted exposure and response prevention (erp) in which family members were involved. Two out of the three patients showed an improvement in ocd-symptoms and for one of these two patients the symptoms went in full remission. These outcomes are promising, and these case studies prove that short erp therapy, which is more intensive and provides assisted erp, can be a possible second step in the treatment.

[An exploratory study of 'blended' cognitive behavioural therapy (CBT) for patients with a panic disorder: results and patients' experiences]. / Een verkennende studie naar blended cognitieve gedragstherapie voor paniek-stoornis: resultaten en patiëntervaringen.

BACKGROUND: Digital technology (e-health or 'blended' care), combined with evidence-based face-to-face CBT, is becoming increasingly implemented into mental health care and is expected to result in improved effectiveness and efficiency. AIM: To explore the feasibility of blended CBT for patients with a panic disorder. METHOD: Nine face-to-face sessions of blended CBT (n = 18), supplemented with the digital support of a tabletcomputer and three e-mail contacts, were compared with 12 weekly sessions of regular CBT (n = 18). Primary outcomes were panic frequency and avoidance behaviour; the secondary outcome was general functioning. Patients' experiences of the treatment were collected in the form of a structured interview. RESULTS: The effect sizes found in both the regular and the blended CBT were medium to high (Cohen's d 0.42-1.60). In both types of treatment there was a significant reduction in patients' symptoms. There were no big differences in patient satisfaction regarding the treatment received. The therapists registered 39 face-to-face minutes in the blended treatment but they registered in total 41 fewer face-to-face minutes; this represented a time reduction of 4%. CONCLUSION: Blended CBT with help of a tablet computer seems to be a suitable method for treating panic disorder psychologically, although the time saved is only moderate. Much more research is needed to ascertain the feasibility and the cost effectiveness of blended CBT.

A high-performance liquid chromatography-tandem mass spectrometry method for the determination of artemether and dihydroartemisinin in human plasma.

A liquid chromatography-tandem mass spectrometry method is described for the quantitative determination of artemether (ART) and its metabolite dihydroartimisinin (DHA) in human plasma samples. Quantitation of ART and DHA in plasma is challenging due to the presence of malaria related hemolytic products in patient plasma causing degradation of the compounds when organic solvents are used during sample processing. Furthermore, both compounds consist of two epimeric forms that can interconvert both in solution and during chromatographic separation, an effect that is dependent on temperature and solvent properties and needs to be taken into account. This method utilizes micro-elution solid-phase extraction as sample preparation technique to minimize the need for organic solvents. Reversed-phase HPLC using a C18 50 × 2.1mm column with 3.5 µm particles and a mobile phase of acetonitrile:water (30:70, v/v), followed by a step gradient at 90% acetonitrile, is applied to separate ART from DHA and matrix interferences within a run time of 4 min. Chromatographic conditions were optimized to allow analyte quantitation independent of the (unknown) ratio of the epimers in the injected sample. A triple quadruple mass spectrometer equipped with an atmospheric pressure chemical ionization interface in positive mode was used for detection in order to detect all epimeric forms. The method proved to be linear over a concentration range of 1.00-1,000 ng/mL using 50 µL of plasma. Accuracy and precision were within 15% for bias and CV (20% at the lower limit of quantification). ART and DHA were stable (bias <15%) in plasma for 211 days after storage at -20°C and -70°C, 17 h on melting ice and 2h at room temperature. Furthermore, both compounds were stable in whole blood after storage for 2h on melting ice and at room temperature and after five freeze/thaw cycles. The method was successfully used for the analysis of pharmacokinetic samples originating from a drug-drug interaction study in which the antimalarial drugs artemether/lumefantrine were coadministrated etravirine or darunavir/ritonavir in healthy human immunodeficiency virus (HIV)-negative subjects.

[The characterisation of anxiety disorders: staging and profiling based on common sense]. / De karakterisering van angststoornissen: stageren en profileren met gezond verstand.

BACKGROUND: Clinicians need to be well informed about staging and profiling so that they can divide patients with anxiety disorders into groups according to the phase and severity of their illness. The group to which the patient is assigned determines the types of treatment he or she receives. AIM: To investigate ways in which clinicians can be helped to apply staging and profiling procedures to patients with anxiety disorders. METHOD: We searched the literature for articles about the staging and profiling of anxiety disorders. RESULTS: There seems to be practically no literature relating to the staging and profiling of anxiety disorders. However, in daily practice clinicians do attempt to classify their patients and use forms of staging when deciding on special types of treatment for their patients and when assessing the length of treatment required. The revised Dutch guidelines on anxiety disorders include a generalised form of staging, called 'stepped care’. These revisions have been made on the basis of consensus decisions reached by the guideline committee. CONCLUSION: The revised guidelines on anxiety disorders assist clinicians with the application of staging in their daily practice. However, because of the lack of scientific data, our article closes with the presentation of a research agenda.

[Treatment of anxiety disorders in the elderly]. / Behandeling van angststoornissen bij ouderen.

AIM: To collect empirical evidence concerning the effectiveness of the treatment of anxiety disorders in the elderly. METHOD: Meta-analysis and randomised controlled trials. RESULTS: Meta-analysis showed that cognitive behavioural therapy (CBT) was more successful than waiting-list control or active control as a treatment for older persons with anxiety disorders. In a direct comparison of the treatment of older persons with panic disorder (PD) both CBT an paroxetine were found to be more effective than waiting-list control. CBT was more successful in reducing avoidance behaviours in older persons with PD. Older persons with reported fewer and less severe agoraphobic cognitions than younger patients, but there was no difference between the severity of agoraphobic avoidance in older patients with PD and younger patients with PD. CONCLUSION: There is sufficient empirical evidence to support the effectiveness of CBT in the treatment of older persons with anxiety disorders. In assessing the severity of PD in the elderly, one should carefully consider the severity of avoidance behaviours. Because no difference was found between the effectiveness of CBT and paroxetine for the treatment of PD in the elderly and because was more effective in reducing avoidance behaviours in older patients with PD than in younger patients with pd, there seems to be a slight preference for CBT in the case of older patients with PD. Older age is not associated with a poorer outcome of treatment with CBT.

[Imaginal exposure treatment for a post-traumatic stress disorder in a patient with a comorbid psychotic disorder]. / Exposurebehandeling voor posttraumatische stressstoornis bij een patiënte met een psychotische stoornis.

A patient suffering from both post-traumatic stress disorder (PTSD) and a comorbid schizoaffective disorder was treated with imaginal exposure treatment. After 26 sessions the ptsd symptoms were in full remission. This was still the case at follow-up after 12 and 24 months. Furthermore, the patient was no longer on antipsychotic medication. The case shows that ptsd can be treated successfully even if patients have a psychotic disorder. In view of the severity of both disorders it is at least worth trying imaginal exposure treatment.

A randomized controlled study of paroxetine and cognitive-behavioural therapy for late-life panic disorder.

OBJECTIVE: To examine the effectiveness of paroxetine and cognitive-behavioural therapy (CBT) in elderly patients suffering from panic disorder with or without agoraphobia (PD(A)). METHOD: Forty-nine patients aged 60+ years with confirmed PD(A) were randomly assigned to 40 mg paroxetine, individual CBT, or to a 14-week waiting list. Outcomes, with avoidance behaviour and agoraphobic cognitions being the primary measures, were assessed at baseline and at weeks 8, 14 (conclusion CBT/waiting list), and at week 26 (treated patients only) and analysed using mixed models. RESULTS: All outcome measures showed that the patients having received CBT and those treated with paroxetine had significantly better improvement compared with those in the waiting-list condition. With one patient (1/20, 5%) in the CBT and three (3/14, 17.6%) in the paroxetine condition dropping out, attrition rates were low. CONCLUSION: Patients with late-life panic disorder respond well to both paroxetine and CBT. Although promising, the outcomes warrant replication in larger study groups.

Differential frontal-striatal and paralimbic activity during reversal learning in major depressive disorder and obsessive-compulsive disorder.

BACKGROUND: Several lines of research suggest a disturbance of reversal learning (reward and punishment processing, and affective switching) in patients with major depressive disorder (MDD). Obsessive-compulsive disorder (OCD) is also characterized by abnormal reversal learning, and is often co-morbid with MDD. However, neurobiological distinctions between the disorders are unclear. Functional neuroimaging (activation) studies comparing MDD and OCD directly are lacking. METHOD: Twenty non-medicated OCD-free patients with MDD, 20 non-medicated MDD-free patients with OCD, and 27 healthy controls performed a self-paced reversal learning task in an event-related design during functional magnetic resonance imaging (fMRI). RESULTS: Compared with healthy controls, both MDD and OCD patients displayed prolonged mean reaction times (RTs) but normal accuracy. In MDD subjects, mean RTs were correlated with disease severity. Imaging results showed MDD-specific hyperactivity in the anterior insula during punishment processing and in the putamen during reward processing. Moreover, blood oxygen level-dependent (BOLD) responses in the dorsolateral prefrontal cortex (DLPFC) and the anterior PFC during affective switching showed a linear decrease across controls, MDD and OCD. Finally, the OCD group showed blunted responsiveness of the orbitofrontal (OFC)-striatal loop during reward, and in the OFC and anterior insula during affective switching. CONCLUSIONS: This study shows frontal-striatal and (para)limbic functional abnormalities during reversal learning in MDD, in the context of generic psychomotor slowing. These data converge with currently influential models on the neuropathophysiology of MDD. Moreover, this study reports differential neural patterns in frontal-striatal and paralimbic structures on this task between MDD and OCD, confirming previous findings regarding the neural correlates of deficient reversal learning in OCD.

Theoretical models in LC based bioanalytical method development.

Bioanalytical method development largely depends on the experience and the preference of the developer. Mathematical models could help in selecting the proper conditions to develop a selective and robust method, using liquid chromatography, liquid-liquid extraction, solid phase extraction and protein precipitation. This paper reviews the literature providing relevant equations and algorithms to model LC based bioanalytical methods for the quantification of small molecules. By using the cited references, it will be possible to build models to describe the analytical methods either as an approximate impression or in a detailed way, incorporating many experimental variables. Special attention has been paid to matrix effects, the most important issues in bioanalysis and possible solutions to handle these issues are discussed. By proper use of the proposed models a more structured method development is accomplished, resulting in a description of the method that could be used for future use to control the complete bioanalytical method.

[Treatment of obsessive-compulsive disorder in older patients - case studies]. / Behandeling van ouderen met een obsessievecompulsieve stoornis.

BACKGROUND: Five patients aged 64 to 74 years with obsessive-compulsive disorder were treated successfully, one with cognitive behavioural therapy and four with a combination of antidepressants and cognitive behavioural therapy. The current multidisciplinary guidelines on anxiety treatment, which cover the age-range 18 to 65 years, are a good starting point for the treatment of obsessive compulsive disorder in older patients.

New practical algorithm for modelling analyte recovery in bioanalytical reversed phase and mixed-mode solid phase extraction.

Solid phase extraction (SPE) is a widely used method for sample cleanup and sample concentration in bioanalytical sample preparation. A few methods to model the retention behaviour on SPE cartridges have been described previously but they are either not applicable to ionised species or are not suitable when using multiple wash and elution steps with solvents differing in volume, modifier concentration and acidity. Furthermore, these models were not applied to mixed mode SPE sorbents. In order to overcome these limitations a new SPE modelling algorithm was proposed. The retention behaviour was determined directly on the SPE cartridge by connecting the cartridge online with an HPLC system using a simple but suitable device that was developed and described. The results from these online experiments were used to model the elution behaviour using a quadratic retention function combined with an exponentially modified Gaussian peak shape model to predict analyte recovery under different wash and elution conditions. The validity of the proposed algorithm was tested using practical SPE experiments with an aqueous test mixture as well as with spiked human plasma. Different sequential wash and elution steps were performed using solvents differing in volume and composition. The predicted band shape and recoveries in each collected step were in good agreement with the results obtained from practical experiments. The proposed algorithm is very useful for the description of the SPE behaviour of the analytes on the actual used SPE cartridge and can be used in structural and automated SPE method development.

Cognitive-behavioural therapy for late-life anxiety disorders: a systematic review and meta-analysis.

OBJECTIVE: To examine and estimate the efficacy of cognitive-behavioural therapy (CBT) for late-life anxiety disorders. METHOD: A systematic review and meta-analysis of randomized controlled trials comparing CBT with i) a waiting-list control condition and ii) an active control condition controlling for non-specific effects in patients aged over 60 years and suffering from an anxiety disorder. The main outcome parameter of individual studies, i.e. effect on anxiety, was pooled using the standardized mean difference (SMD). RESULTS: Seven papers fulfilled the inclusion criteria, including nine randomized controlled comparisons for 297 patients. Anxiety symptoms were significantly more reduced following CBT than after either a waiting-list control condition [SMD = -0.44 (95 CI: -0.84 -0.04), P = 0.03] or an active control condition [SMD = -0.51 (95 CI: -0.81, -0.21), P<0.001]. Additionally, CBT significantly alleviated accompanying symptoms of worrying and depression. CONCLUSION: Cognitive-behavioural therapy is efficacious for the treatment of late-life anxiety disorders.

pH adjustment of human blood plasma prior to bioanalytical sample preparation.

pH adjustment in bioanalytical sample preparation concerning ionisable compounds is one of the most common sample treatments. This is often done by mixing an aliquot of the sample with a proper buffer adjusted to the proposed pH. The pH of the resulting mixture however, does not necessarily have to be the same as the pH of the used buffer due to the significant buffer capacity of the sample. Calculation methods from titration technology were adapted and applied to this problem. The acid-base characteristics of human blood plasma and serum samples were determined and used to calculate the pH of buffer-plasma mixtures. Based on these parameters and the characteristics of the used buffers, two alternative methods were described to prepare buffers that lead to the proposed pH when mixed in the right volume ratio with human plasma samples. The resulting pH of several mixtures of different buffers with human blood plasma were in good accordance with the calculated pH. The proposed calculation methods and recommended buffer preparation methods may lead to more robust bioanalytical methods.

Reconsideration of sample pH adjustment in bioanalytical liquid-liquid extraction of ionisable compounds.

Liquid-liquid extraction (LLE) is widely used as a simple and robust sample preparation technique in bioanalytical sample preparation. When extracting ionisable compounds, most bioanalysts adjust the pH of the sample to achieve fully unionized compounds. Usually, a generally accepted rule is applied to adjust the pH of the aqueous phase, known as the pKa+/-2 rule, depending on the acid/base characteristics of the analyte. By taking a closer look at the general equations that describe the extraction behaviour of ionisable compounds, we extended this pH adjustment rule by taking the distribution ratio and the volume of both liquid phases into account. By choosing an extraction pH based on this extended rule, the selectivity of the extraction can be influenced without loss of recovery. As a measure of this selectivity, two equations were proposed to indicate the ability of the extraction system to discriminate between two compounds. Also, milder extraction pH can be used for pH labile analytes. To use this new rule quantitatively, a new calculation method for the determination of the distribution ratio was derived. These calculations were based on normalized recoveries making this method less susceptible to errors in absolute recovery determination. The proposed equations were supported by demonstrating that careful pH adjustment can lead to higher selectivity. The main conclusion was that a closer look at the extraction pH in bioanalytical methods extends the possibilities of obtaining a higher selectivity or the possibilities of extracting pH labile analytes at milder pH conditions without loss of recovery.