Meta-analysis of cognitive behaviour therapy and selective serotonin reuptake inhibitors for the treatment of hypochondriasis: Implications for trial design.

BACKGROUND: Classification of hypochondriasis as an obsessive-compulsive and related disorder in the International Classification of Diseases 11th Revision (ICD-11) has generated new heuristics for treatment of this common, chronic and disabling disorder. Standard treatment involves cognitive behaviour therapy (CBT) or selective serotonin reuptake inhibitors (SSRIs), but no meta-analysis has so far considered hypochondriasis as a structured diagnosis or assessed the role of medication. A clearer understanding of the relative effectiveness of these interventions and identification of clinically relevant factors moderating the treatment response is needed for clinical guideline development. METHODS: The current systematic review and meta-analysis of interventions for hypochondriasis was preregistered on PROSPERO (CRD42020185768) and follows PRISMA guidelines. We searched MEDLINE, PsycINFO, and Cochrane Library databases until July 2021 for randomized controlled trials (RCTs) of interventions for patients diagnosed with hypochondriasis (or historical diagnostic equivalents). We assessed aspects of study quality using: the CONSORT Checklist for evaluation of RCTs, the Cochrane Risk of Bias 2 tool, researcher allegiance and treatment fidelity. The primary outcome was improvement in hypochondriasis symptoms, comparing intervention and control groups at trial endpoint. Moderator variables were assessed using subgroup and meta-regression analyses. RESULTS: Searches identified 13 randomised controlled trials (RCTs) (N = 1405); 12 included CBT (N = 1212) and three included SSRI (N = 193) arms as the experimental intervention. Random effects meta-analysis yielded a moderate-to-large effect size for CBT versus all controls (g = -0.70 [95% CI -0.99 to -0.41], k = 18, I2 = 81.1%). Funnel plot asymmetry indicated possible publication bias and two potentially missing trials, reducing the effect size (g = -0.60 [95% CI -0.88 to -0.32]). Subgroup analysis showed that choice of control significantly moderated effect size, with those in CBT vs. wait-list (g = -1.32 [95% CI -1.75 to -0.90], k = 7, I2 = 0%) being double those of CBT vs. psychological or pharmacological placebo controls (g = -0.58 [95% CI -0.95 to -0.22], k = 7, I2 = 82%). Analysis of studies directly comparing CBT and SSRIs found a numerical, but not statistical advantage for SSRIs (g = 0.21 [95% CI -0.46 to 0.87], k = 2, I2 = 58.34%) and a modest effect size emerged for SSRIs vs. pill placebo (g = -0.29 [95% CI -0.57 to -0.01], k = 3, I2 = 0%). Most studies (11/13) were rated as high on potential researcher allegiance bias in favour of CBT. Meta-regressions revealed that effect sizes were larger in younger participants, and smaller in better quality and more recent RCTs and those with greater CBT fidelity. CONCLUSION: CBT and SSRIs are effective in the acute treatment of hypochondriasis, with some indication that intervention at a younger age produces better outcomes for CBT. In the case of CBT, effect sizes appear to have been significantly inflated by the use of wait list controls, and researcher allegiance bias. We recommend that a definitive, adequately controlled trial, designed with respect to the methodological issues raised in this meta-analysis, is needed to determine the magnitude effects for CBT and SSRIs with confidence and the long-term effect of treatments, to inform mental health service provision for this overlooked patient group.

Hypochondriasis: treatment options for a diagnostic quagmire.

OBJECTIVE: This article presents the conceptual and diagnostic conundrums surrounding hypochondriasis and reviews current treatment options for this disorder. CONCLUSIONS: The removal of hypochondriasis from the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition and its replacement with two new diagnostic entities have been controversial. It appears that the Eleventh Revision of the International Classification of Diseases will take a more cautious approach and emphasise the links between hypochondriasis, obsessive-compulsive disorder and other anxiety disorders. The cornerstone of any treatment approach to hypochondriasis is establishing a good therapeutic relationship with the patient. Psychological treatments, especially cognitive-behavioural therapy, have been more useful than pharmacotherapy, but there is much room for improving treatment outcomes.

["Factitious disorder and skin picking: Clinical approach". A case report]. / Trouble factice et dermatillomanie : approche clinique. À propos d'un cas.

OBJECTIVE: The number of patients requiring primary and secondary care for factitious disorder unexplained by any known medical condition is high. We report a case illustrating the clinical and psychopathological features of factitious disorder. The treatment difficulties encountered in the association of this disorder with dermatillomania are discussed. CASE REPORT: The patient was a 22-year old girl with abrasions on the face and forearms with ingested epidermal layer of the skin. She also had multiple somatic complaints, the authenticity of which was difficult to confirm. The diagnosis of comorbid factitious disorder with dermatillomania was retained. In view of reducing self-harm acts, we prescribed a mood stabilizer associated with an anxiolytic for 6 months. The self-harming acts have regressed, while the hypochondriacal complaints remain with a tendency of overstatement. DISCUSSION: Factitious disorder (FD) is a mental disorder occurring in patients acting intentionally similar to a physically or mentally sick person with no apparent benefits. The reported cases often show FD comorbidity with other psychiatric disorders such as substance abuse, somatoform disorders, dysthymia, borderline personality disorder and sexual disorders. Comorbidity of factitious disorder with neurotic excoriation is exceptional, and rarely described in the literature. Pathological skin picking (PSP) is a disabling disorder characterized by repetitive skin picking, which causes tissue damage. It was estimated to affect 2% of the population. PSP is currently listed as an impulse control disorder not otherwise specified, it is associated with a high rate of psychiatric comorbidity like borderline personality disorder. CONCLUSION: The comorbidity of factitious disorder and dermatillomania makes diagnosis very difficult. The limit between the two disorders is sometimes unclear.

Long-term follow-up of hypochondriasis after selective serotonin reuptake inhibitor treatment.

BACKGROUND: : There is paucity of knowledge on the long-term outcome of hypochondriasis, with even less knowledge about the effect of treatment with a selective serotonin reuptake inhibitor (SSRI). METHODS: : This prospective follow-up study included 58 patients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) hypochondriasis who had participated in a trial of SSRI treatment 4 to 16 years earlier (mean ± SD = 8.6 ± 4.5 years). RESULTS: : Information was obtained on 79.3% (n = 46) of the original group. At follow-up, 40% of the patients continued to meet full DSM-IV criteria for hypochondriasis. Persistence of hypochondriasis was individually predicted by longer duration of prior hypochondriasis (P = 0.003), history of childhood physical punishment (P = 0.01), and less usage of SSRIs during the interval period (P = 0.02). Remission status was not significantly predicted by demographic characteristics, baseline hypochondriasis severity, or psychiatric comorbidity. CONCLUSIONS: : A substantial proportion of patients with hypochondriasis who receive treatment with SSRIs achieve remission over the long term. Interim SSRI use may be a factor contributing to better prognosis.

A double-masked, placebo-controlled study of fluoxetine for hypochondriasis.

This study assessed the efficacy, durability, and tolerability of fluoxetine for hypochondriasis, a disorder for which controlled pharmacological trials are scarce. Fifty-seven patients with hypochondriasis were enrolled: 12 discontinued during the placebo run-in, and 45 were randomized to either fluoxetine or placebo for 12 weeks (acute treatment). Responder status was defined as a Clinical Global Impression rating for hypochondriasis of much or very much improved. Secondary outcome measures included severity of hypochondriasis, somatization, anxiety, and depression. Responders to acute treatment entered a 12-week maintenance phase to week 24. Sustained responders at week 24 entered a 12-week double-masked discontinuation phase. Primary analysis used the intent-to-treat sample. More patients responded with improvement in hypochondriasis when given fluoxetine compared with placebo, starting at week 8 (50.0% vs 19.0%, P = 0.03) and continuing to week 12 (62.5% vs 33.3%, P = 0.05). Mean dose at week 12 dose was 51.4 mg (SD, +/-23 mg). The acute treatment response was maintained to week 24 with more responders in the fluoxetine compared with the placebo group (54.2% vs 23.8%, P = 0.04). Significant improvement was not noted on the continuous secondary outcomes measures of hypochondriasis, with the exception of the Clinical Global Impression hypochondriasis severity scale at week 24. Likelihood of response was not associated with severity of psychiatric comorbidity. Durability of response after controlled drug discontinuation could not be reasonably assessed, given the small sample size of patients who entered the discontinuation phase (n = 10). Fluoxetine was well tolerated, with no significant differences in discontinuation due to side effects between treatment groups. Fluoxetine is a moderately effective and well-tolerated treatment for hypochondriasis.

[Hypochondrical paranoia].

This is a case report of hypochondrical paranoia in a young man, who was convinced of a toxic infection by fungi following mold growth exposure. The patient was admitted to a psychiatric facility, severely pained by the delusional perception of his insides being eaten by fungus. He had undergone a thorough medical examination without the discovery of any somatic irregularities and had attempted to treat himself several times. After four months of hospital-ization and the prescription of antipsychotic treatment, he was in recovery. Mild delusions persisted but were no longer pathologically painful.

Antidepressant treatment outcomes of psychogenic movement disorder.

BACKGROUND: Psychogenic movement disorder (PMD) is a subtype of conversion disorder. We describe the outcomes of a series of PMD patients following antidepressant treatment. METHOD: Twenty-three outpatients with chronic PMD, diagnosed using Fahn and Williams' criteria, underwent psychiatric assessment. The patients were referred for assessment and management from January 2003 to July 2004. Fifteen agreed to be treated with antidepressants. Patients received citalopram or paroxetine; those who did not respond after 4 weeks of taking an optimal dose were switched to venlafaxine. Concurrently, 3 had supportive psychotherapy, and 1 had family intervention. Assessments included the DSM-IV-based Mini-International Neuropsychiatric Interview and scales measuring depression, anxiety, and motor and global severity. RESULTS: Eighteen patients (78%) had at least 1 Axis I diagnosis in addition to the somatoform diagnosis, and 3 (13%) had somatization disorder. Five (22%) had previous psychiatric contact. Nine (39%) had previously been treated with antidepressants, but only 4 (17%) had adequate trials. No significant differences existed in patient characteristics between treated and untreated groups. Among treated patients, Montgomery-Asberg Depression Rating Scale scores improved from baseline (p < .01). Two treated subgroups were identified: 10 patients (67%) had primary conversion disorder, of whom 8 had marked motor and global improvements with 7 complete remissions, and 5 (33%) had primary hypochondriasis, somatization disorder, or probable factitious disorder/malingering, of whom none improved. All of the patients with primary conversion disorder had a current or previous depressive or anxiety disorder compared with 40% (N = 2) of the patients with additional somatoform diagnoses. DISCUSSION: Our preliminary findings suggest that chronic PMD with primary conversion symptoms and with recent or current depression or anxiety may respond to antidepressants. Further well-designed studies, now under way, are required to confirm these findings.

Treatment of endogenous anxiety with phobic, hysterical, and hypochondriacal symptoms.

Endogenous anxiety (anxiety hysteria, agoraphobia with panic attacks) is characterized by sudden, spontaneous panic attacks accompanied by multiple autonomic symptoms, overwhelming fear, a flight response, and polyphobic behavior. Psychotherapy, behavior therapy, and tranquillizers have been of limited success in treating this syndrome. Fifty-seven patients severely disabled by the syndrome for a mean period of 13 years completed the three-month study. Randomly assigned in a double-blind, placebo-controlled design to imipramine hydrochloride, pheneizine sulfate, or placebo, they were seen in supportive group therapy every two weeks. Patients in the pheneizine and imipramine cells showed significant improvement ovehe persistent trend for pheneizine to be superior to imipramine achieved significance only on the Work and Social Disability Scale and the Sympton Severity and Phobic Avoidance Scale. The implications for classification and theory are discussed.

Monosymptomatic hypochondriasis treated with tricyclic antidepressants.

The authors report on two patients with disabling monosymptomatic hypochondriasis who responded to tricyclic antidepressants. They include a brief review of the literature on this uncommon debilitating illness.

Hypochondriasis and obsessive compulsive disorder: overlaps in diagnosis and treatment.

BACKGROUND: Hypochondriasis is a disorder for which there are no established effective treatments. Hypochondriacs, in their obsessions about illness, compulsions to check with others, and failure to be reassured, share many features in common with those who have obsessive compulsive disorder (OCD). METHOD: The authors present a case series of six patients with DSM-III-R hypochondriasis, five of whom also had a history of OCD. Two of the six agreed to be treated with doses of fluoxetine typically used to treat OCD. RESULTS: Both patients, one of whom had no past history of OCD, showed a marked improvement in hypochondriacal symptoms. CONCLUSION: These findings suggest that a subgroup of patients with hypochondriasis may be particularly responsive to serotonin reuptake blockers.

Monosymptomatic hypochondriacal psychosis manifesting as delusions of infestation: case studies of treatment with haloperidol.

Pimozide has been successfully used in the treatment of delusions of infestation; however, it is not widely available in the United States. Similarities in both chemical structure and degree of potency suggest that haloperidol may be an alternative treatment for this syndrome. Three cases of delusions of infestation successfully treated with haloperidol are described. In all three the symptoms were relieved acutely; in two the improvement was maintained.

Epidemiology and treatment of hypochondriasis.

Although hypochondriasis has been one of the most durable disease concepts in psychopathology, little is known about its epidemiology and treatment. In this article, we review the last three decades of research into these two aspects of hypochondriasis. According to DSM-IV, hypochondriasis is a distressing preoccupation with the fear or thought, based on physical sensations, that one has a serious disease. The prevalence of hypochondriasis in the general population is unknown; however, studies in primary care suggest that the prevalence in this setting is between 0.8 and 4.5%. There are, at present, no conclusive data about specific risk factors for hypochondriasis, although patients with hypochondriasis have higher rates of anxiety, depressive and other somatoform disorders than patients without the disorder. To date, there have been no studies documenting a genetic or familial predisposition for hypochondriasis, or for somatoform disorders in general. Cognitive behavioural therapy has been shown in controlled studies to be efficacious in the treatment of hypochondriasis. Although the evidence is stronger for individual therapy, group cognitive-behavioural therapy may also be useful. Other therapies such as supportive or psychoanalytical psychotherapy may be efficacious for certain patients, but the lack of standardised treatments and controlled studies makes them a less preferable treatment option at present. Little is known about the pharmacological treatment of primary hypochondriasis. The limited number of published studies and the absence of controlled trials make it impossible to be certain of the efficacy of existing medications. On the basis of the available information, however, it appears that the selective serotonin reuptake inhibitors hold promise for the treatment of this disorder. However, more information is needed for their efficacy to be clearly established.

Monosymptomatic hypochondriacal psychosis manifesting as delusions of parasitosis. A description of four cases successfuly treated with pimozide.

A recent article in the Archives described the severe problems encountered in trying to treat patients with delusions of parasitosis. The present article describes four such cases, which fall into the larger category of monosymptomatic hypochondriacal psychoses, conditions that appear to be related to the paranoid disorders. Evidence is accumulating that such cases may respond very specifically to treatment with pimozide, a relatively new psychotropic medication. This drug keeps the symptoms in remission but does not effect a cure; nevertheless, it may represent a highly important advance in therapy in a condition traditionally regarded as virtually untreatable.

An open study of paroxetine in hypochondriasis.

1. Despite the high prevalence of hypochondriasis, this disorder is found to be the focus of research only minimally. 2. This open study evaluates the efficacy and tolerance of paroxetine in 11 patients with DSM-III-R hypochondriasis. 3. Using paired samples t-test, a significant reduction on measures of hypochondriasis was found after 12 weeks of treatment compared to baseline. Two patients dropped out prematurely. At post-test, eight out of nine patients who completed the study had improved to a clinically relevant degree. Of these, five attained scores in the reach of the normal population. 4. In one patient who completed the study and one patient who dropped out, tolerance of paroxetine was poor, whereas in remaining patients tolerance was moderate to good. 5. The results of this study suggest that patients with hypochondriasis may be responsive to paroxetine. A controlled study is recommended.

A double-blind controlled trial of amineptine versus trimipramine in depression.

A double-blind controlled trial was carried out in 50 depressed out-patients to compare the effectiveness and tolerability of amineptine (200 mg per day) with that of trimipramine (75 mg per day). Patients were allocated at random to receive one or other of the trial drugs over a period of 45 days. Assessments were made before, during and after treatment of a number of target symptom clusters. Whilst overall response to treatment was the same with both drugs, trimipramine was superior in those patients presenting with anxiety and insomnia. Amineptine, however, was more effective not only against depressive mood and psychomotor retardation, but also against loss of libido, hypochondriacal features and social withdrawal. Both drugs were relatively well tolerated, but trimipramine had a sedative effect which proved troublesome in some patients.

Hypochondriasis and its relationship to obsessive-compulsive disorder.

Hypochondriasis is a heterogeneous disorder. This was well demonstrated in the study by Kellner et al, which showed that patients with high levels of disease fear tended to be more anxious or phobic, whereas patients with high levels of disease conviction tended to have more and more severe somatic symptoms. Little comorbidity exists to support the statement that hypochondriasis is an obsessive-compulsive spectrum disorder. Although patients exist whose hypochondriac concerns are identical in quality to the intrusive thoughts of patients with OCD, as a group, patients with hypochondriasis do not share a comorbidity profile comparable with that of patients with OCD. The data support a closer relationship between hypochondriasis and somatization disorder than between hypochondriasis and OCD. The family history data is limited by the lack of adequate studies. Using comparable methods of the family history approach, Black's study reported a higher frequency of GAD but not OCD among the relatives of OCD patients--a finding similar to what Noyes found among the relatives of hypochondriac patients; however, using the direct interview method, somatization disorder was the only statistically more common disorder, among relatives of female hypochondriac patients. Therefore, although the parallel in overlap with GAD is suggestive of a commonality between OCD, GAD, and hypochondriasis, the finding of a greater frequency of somatization disorder leans against the hypothesis that hypochondriasis is best considered an OCD spectrum disorder. The pharmacologic treatment data are the one type of biologic evidence that supports a bridge to OCD. The pharmacologic studies suggest that for patients with general hypochondriasis, TCAs are not effective and that higher dosages and longer trials of the SRIs are needed. These pharmacologic observations are comparable with the ones made for patients with OCD but dissimilar to the observations made for depression. The benefit of imipramine among patients with illness phobia must be assessed in placebo-controlled trials among illness phobics and among hypochondriacs. Even more valuable would be a direct comparison of a TCA (e.g., imipramine or desipramine) and a selective SRI (e.g., fluoxetine) to determine whether the response to selective SRIs is greater. Although the pharmacologic data are compelling in supporting the hypothesis that hypochondriasis is an obsessive-compulsive spectrum disorder, the comorbidity data are equally compelling in dispelling that hypothesis. Perhaps future studies clarify the subtypes of hypochondriasis, be they "phobic, obsessive, and depressive," "chronic and episodic," "early onset versus late onset" or some other as yet undetermined subtype. Such clarification may be aided by better instruments to assess the obsessive-compulsive and hypochondria spectrums within individuals and families and by neuropsychological or pharmacologic challenge and neuroimaging studies.

Pimozide in dermatologic practice: a comprehensive review.

Pimozide is an antipsychotic drug of the diphenylbutylpiperidine class. In the US, it is FDA-approved only as a backup treatment for Gilles de la Tourette syndrome, although it has been used in other countries for many years as a treatment for schizophrenia. In the past 20 years, pimozide has been found to be especially efficacious in the treatment of monosymptomatic hypochondriacal psychoses and is used by psychiatrists and dermatologists for this off-label purpose. In particular, pimozide is considered the treatment of choice for delusions of parasitosis. In addition, pimozide has been found to be efficacious in the treatment of body dysmorphic disorder, metastatic melanoma, trichotillomania, and trigeminal and postherpetic neuralgia. This review aims to familiarize physicians, especially dermatologists, on the uses of pimozide in dermatologic practice. A review of the literature was performed and the relevant information synthesized to give a complete overview of the drug and its therapeutic uses in dermatology.