Antonio Tundo

Psychopathology, Temperament, and Past Course in Primary Major Depressions. 1. Review of Evidence for a Bipolar Spectrum

In reviewing recent findings on affective conditions in the interface of unipolar and bipolar disorders, we find evidence favoring a partial return to Kraepelins broad concept of manic-depressive illness, which included many recurrent depressives and temperamental variants. This review addresses methodologic, clinical, and familial considerations in the definition and characterization of a proposed spectrum of bipolar disorders which subsumes episodic and chronic forms. Episodic bipolar disorders are subclassified into bipolar schizoaffective, and bipolar I and II, and bipolar III or pseudo-unipolar forms. Chronic bipolar disorders could be either intermittent or persistent, and are subclassified into chronic mania, protracted mixed states, and rapid-cycling forms, as well as the classical temperaments (cyclothymic, hyperthymic, irritable and dysthymic).

Derealization and panic attacks: a clinical evaluation on 150 patients with panic disorder/agoraphobia.

One hundred fifty patients with Panic Disorder (PD) with or without Phobic Avoidance were subdivided into two groups on the basis of presence/absence of derealization and/or depersonalization (D-D) during panic attacks. D-D was found in 34.7% of the sample. By comparing the two groups, the patients with D-D were found to be younger and had an earlier onset of the disorder; they had a higher prevalence of avoidance behavior and a higher severity of the agoraphobic spectrum phobias. They were also more frequently subject to concomitant disorders such as Generalized Anxiety, Obsessive-Compulsive, and depressive symptomatology. The authors have hypothesized a correlation between the presence of D-D during panic attacks and a more frequent clinical evolution toward agoraphobia. This view is supported by finding that D-D in panic attacks corresponds to severer forms of PD, both in terms of the earlier onset of PD, and because PD shows higher levels of anxiety, depression, and disability.

Cognitive-behavioral therapy for obsessive-compulsive disorder as a comorbidity with schizophrenia or schizoaffective disorder.

of OCD was 6.8 years (range 1–16.7). The temporal onset of OCD was subsequent to SCH/SA in 11 patients (6 SCH, 5 SA), anterior in 3 SA patients and concomitant in 7 patients (3 SCH, 4 SA). Four patients presented at least one other Axis I lifetime comorbid disorder. Pharmacological treatments for SCH/SA were chosen by the first author (A.T.) based on the patient’s clinical condition, and follow-up visits were scheduled as required, ranging from every week to every few months. CBT was conducted by 4 cognitivebehavioral psychologists with 6 5 years of experience in treating OCD. CBT consisted of imaginal and in vivo exposure, ritual prevention and/or delay, cognitive therapy and other ad hoc intervention used to supplement exposure and ritual prevention strategies. Patients were treated in a naturalistic setting, in the sense that manualized guidelines [33] were adapted to each patient after careful consideration of their level of insight, treatment adherence and Axis I comorbidity. Therapy sessions were scheduled flexibly and jointly by the therapist and patient. Patients received an average of 4 sessions per month during the first 4 months and then continued therapy with 1–4 sessions per month. CBT duration was not determined in advance. We provided a mean of 34.3 h of therapy (range 23–41) to patients with SA and 31.1 h (range 8–40) to patients with SCH, excluding 1 patient who participated in a single session before withdrawing from the study. Obsessive-compulsive symptoms were assessed using the Y-BOCS. The clinical severity of illness was assessed using the Clinical Global Impressions-Severity (CGI-S) scale [34] and overall functioning using the Global Assessment of Functioning scale [35] . Scales were administered at baseline (T0) and after 6 (T1) and 12 months (T2) of CBT. The Clinical Global Impressions-Improvement (CGI-I) scale [34] was used to evaluate improvement at T1 and T2. Schizophrenic and schizoaffective symptoms at T0 were assessed using the Positive and Negative Symptoms Scale. All assessments were conducted by the first author, who was not involved in the CBT. The primary outcomes were adherence rate (percentage of completers) and remission rate (Y-BOCS total score ! 16). Secondary outcomes were treatment response, defined as a decrease in the Y-BOCS total score from baseline to T2 6 25%, and a CGI-I score ̂ 2. One patient with SCH discontinued CBT after 1 session; 1 patient with SCH discontinued before T1 and 3 patients (1 SCH, 2 SA) before T2. Of these, 3 reported that CBT was ineffective and 1 was hospitalized for an episode of psychotic exacerbation. The remaining 16 patients were still receiving CBT at T2. Table 1 shows the results of repeated-measures ANOVA for Y-BOCS and the CGI-S and the Global Assessment of Functioning scales. All outcome measures showed statistically significant improvements at 6 months and slower improvement afterwards. There was no differential change over time in SA versus SCH, except for a significantly greater functional improvement in SA from T0 to T1. At T2, 52% of patients (11/21) were rated as ‘much/ The co-occurrence of obsessive-compulsive disorder (OCD) in patients with schizophrenia (SCH) or schizoaffective disorder (SA) is quite common (7.8–25%) [1–6] . Obsessive-compulsive symptoms in patients with SCH are associated with severe psychosis, a high risk of suicide, severe impairment of social behavior and a poor prognosis [7–12] . Despite the high prevalence and disabling effects of OCD-SCH/SA comorbidity, only a few studies have investigated treatment strategies for this difficult-to-treat condition. The best current available treatments for noncomorbid OCD are serotonin reuptake inhibitors (SRIs) and cognitive-behavioral therapy (CBT) incorporating exposure and ritual prevention [13] . The American Psychiatric Association guidelines [13] and Poyurovsky et al. [14] suggest treating OCD co-occurring with SCH by combining either typical or atypical antipsychotics with SRIs. However, evidence on the beneficial effect of these combinations is inconclusive [15–27] . Furthermore, an antipsychotic-SRI combination could produce a clinically significant pharmacokinetic drug interaction. Hence, alternative therapeutic approaches for OCD-SCH/SA are needed. The aims of this open naturalistic study were to examine adherence to and the effectiveness of adjunctive CBT for OCD in patients with stabilized SCH/SA. Consecutive patients seen between 1 January 2003 and 1 January 2008 at the ‘Istituto di Psicopatologia’ in Rome were screened for eligibility. Inclusion criteria were as follows: (1) age 18–65 years; (2) meeting DSM-IV criteria for OCD and either SCH or SA as assessed by the Structured Clinical Interview for DSM-IV [28, 29] ; (3) OCD of at least moderate severity [Yale-Brown Obsessive Compulsive Scale (Y-BOCS) [30, 31] total score 6 16], and (4) stabilized SCH or SA, even if symptoms were not entirely absent (Positive and Negative Symptoms Scale [32] total score ̂ 75). The exclusion criterion was the presence of neurological conditions inducing OCD. All patients gave written informed consent for the anonymous use of their clinical records, and a local ethical committee approved the research project. Twenty-one patients (13 males, 8 females) were enrolled; the mean age was 29.3 years (range 18–37). Nine patients (43%) had SCH and 12 (57%) SA. The mean duration Received: December 20, 2010 Accepted after revision: May 17, 2011 Published online: November 25, 2011

Onset polarity and illness course in bipolar I and II disorders: The predictive role of broadly defined mixed states

Several studies investigating bipolar disorders have shown that polarity of onset can predict differences in symptomatology, course, and prognosis. Frequently, however, research on the topic has examined only bipolar I inpatients and has not included patients with mixed onset. The aim of the present naturalistic study was to evaluate the clinical characteristics and illness course of a consecutive sample (407 outpatients, 58.7% with bipolar I (BD-I) and 41.3% with bipolar II (BD-II) disorder) according to polarity of onset: depressive (DP-o); manic/hypomanic (HM-o); or mixed--broadly defined to include agitated depression for BD-II--onset (MX-o). As compared with patients in the other two groups: a) DP-o patients (67.3%) were more frequently affected by BD-II and had lower ratings for psychotic symptoms; b) HM-o patients (17%) had a higher rate of family history for psychosis and a lower rate of suicide attempts; and c) patients in the MX-o group (15.7%) more frequently showed substance abuse and had a higher number of mixed recurrences per year. In the BD-II group, MX-o patients more frequently attempted suicide. The present studys main limitations are those of retrospective assessment of onset polarity and lack of treatment-impact evaluations over illness course. In conclusion, we confirm clinical expression differences in bipolar disorder in function of polarity of onset and underscore the importance of carefully considering broadly defined mixed state when examining polarity of onset. Further investigations are required to confirm the present studys results.

Short-term antidepressant treatment of bipolar depression: Are ISBD recommendations useful in clinical practice?

OBJECTIVES The study aimed to test the effectiveness of the ISBD Guidelines for short-term AD treatment of BP depression. METHODS The study sample included 255 patients with mood disorders (154 UP, 49 BP-I, 52 BP-II). Response was defined as a HDRS21 total score<7 at 12 weeks of treatment and remission as a ≥50% reduction of baseline HDRS21 total score sustained for 8 weeks. RESULTS Response was achieved by 64.9% of patients with UP disorder, 75.5% of patients with BP-I disorder and 75.0% with BP-II disorder without significant differences (χ²=3.0, p=0.219). The remission rate did not differ significantly among groups (χ²=3.8, p=0.151). The dropout rate was significantly higher for patients with UP (18.2%) than for patients with BP-I (2%) and BP-II (7.7%) disorder (χ²=10.1, p=0.006). Concerning AD safety, one patient with BP-I depression committed a suicide attempt and AD-emerging switch was observed in 2.9% of patients, 2 with BP-I and 1 with BP-II disorder. LIMITATIONS The observational nature of the study and unblinded outcomes assessment. CONCLUSIONS Our findings confirm the usefulness of ISBD Guidelines for short-term AD treatment of BP depression. These patients appear to have similar response and remission rate to those observed in UP depression and do not exhibit significant switch rates or risk of suicide. Our results are limited to patients with pure bipolar depression (excluding those with broadly defined mixed states), treated with ADs-mood stabilizers combination. We suggest to partially modify ISBD Recommendations 1 and 4, to include potential responders and to improve safety.

Effectiveness of cognitive-behavioral therapy addition to pharmacotherapy in resistant obsessive-compulsive disorder: a multicenter study.

day of citalopram, fluoxetine, and paroxetine, 6 100 mg/day of clomipramine, 6 20 mg/day of escitalopram, 6 200 mg/day of fluvoxamine and sertraline, and 6 250 mg/day of venlafaxine. Exclusion criteria were a lifetime diagnosis of schizophrenia or other psychotic disorders, mental retardation, or an organic brain syndrome. All patients gave written informed consent, and a local ethical committee approved the research project. Patients maintained the same drug and dosage while CBT was added (exposure and response prevention; cognitive therapy and other ad hoc interventions were used when necessary). Patients were treated in a naturalistic setting in the sense that manualized guidelines [18] were adapted to each patient by taking due account of the insight level into the senselessness of OCD symptoms, treatment adherence, and the presence of Axis I disorders. The therapist and the patient scheduled therapy sessions flexibly and jointly. CBT duration was not fixed in advance. The primary outcome was Y-BOCS change from the beginning of CBT to the endpoint. CGI-S and GAF scores (although poorly validated) were also used. Response was defined as a Y-BOCS decrease 6 25% and remission as a Y-BOCS decrease

Parsing the phenotype of obsessive-compulsive tic disorder (OCTD): a multidisciplinary consensus

Abstract Obsessive-Compulsive Disorder (OCD) and Tic Disorder (TD) are highly disabling and often comorbid conditions. Of note, the DSM-5 acknowledged a new ‘tic-related’ specifier for OCD, which might be referred to as Obsessive-Compulsive Tic Disorder (OCTD), raising new interest toward a better clinical characterisation of affected patients. Available literature indicates that early onset, male gender, sensory phenomena and obsessions of symmetry, aggressiveness, hoarding, exactness and sounds as well as comorbidity with Attention Deficit Hyperactivity Disorder (ADHD) may be of more frequent observation in patients with OCTD. In order to share expertise in the field from different perspectives, a multidisciplinary panel of Italian clinicians, specifically involved in the clinical care of OCD and TD patients, participated into a consensus initiative, aimed to produce a shared document. As a result, after having examined the most relevant literature, authors sought to critically identify and discuss main epidemiologic, socio-demographic and clinical features characterising OCTD patients, along with other specific aspects including Health-Related Quality-of-Life (HRQoL), economic consequences related with the condition and its management, as well as treatment-related issues, that need to be further investigated.

Continuous circular cycling in bipolar disorder as a predictor of poor outcome

OBJECTIVE This prospective study aims to determine if patients with bipolar disorder with a continuous circular course (CCC) are significantly different on clinical characteristics and response to long-term treatment from those with a non-continuous circular course (N-CCC). CCC was defined as the alternation of depression and (hypo)mania without a completely free interval, and N-CCC as the presence of free intervals after the sequence mania-depression or depression-mania. METHOD The study sample includes 140 consecutive patients with bipolar I or II disorder according to DSM-IV criteria, aged 18-65 years and receiving prophylactic treatment for. Treatment was based upon international guidelines and clinical experience at the time of patients enrollment (from January 1998 to January 2006). Primary outcome was the absence of new episodes during the follow-up. Significance level was set at p<0.05. RESULTS Twenty-eight percent of the sample has CCC. Compared with N-CCC, CCC patients were older, had a later onset, a higher number of total, depressive and (hypo)manic episodes, and of switches, and spent a higher percentage of time ill in the year before entering the study. Polarity at onset and subsequent recurrences were more frequently mixed in N-CCC than in CCC patients. The proportion of patients in the CCC group who had no recurrences during the follow-up was significantly lower than in the N-CCC group. CONCLUSION The presence or absence of a free intervals over the course of illness identifies two subtypes of bipolar disorder that differ in clinical presentation, outcome, and response to long-term treatment.

Cognitive-behavioural therapy for obsessive-compulsive disorder co-occurring with psychosis: Systematic review of evidence

AIM To review available evidence on the use of cognitive behavioural therapy (CBT) for treating obsessive compulsive disorder co-occurring with psychosis. METHODS In this paper we present a detailed and comprehensive review of the current literature focusing on CBT treatment of obsessive compulsive disorder (OCD) co-occurring with schizophrenia or schizoaffective disorder. We identified relevant literature published between 2001 and May 2016 through MEDLINE/PubMed search using as search string (“obsessive compulsive disorders” or “obsessive compulsive symptoms”) and (“schizophrenia” or “schizoaffective disorder” or “psychosis”) and (“cognitive behavioural therapy”). Other citations of interest were further identified from references reported in the accessed articles. The search was limited to studies written in English and carried out in adult patients. A total of 9 studies, 8 case reports and 1 case series, were found. RESULTS The reviewed evidence indicates that CBT is: (1) safe, i.e., does not worsen psychotic symptoms; (2) well accepted, with a discontinuation rate quite similar to that reported for patients with OCD without psychosis comorbidity; (3) effective, with a symptom reduction quite similar to that reported for patients with OCD without psychosis and for SRIs treatment of OCD co-occurring with psychosis; and (4) effective in patients with OCD induced by second-generation antipsychotic as well as in patients with OCD not induced by second-generation antipsychotic. Alcohol/substance use disorder comorbidity and OCD onset preceding that of SCH/SA was predictors of poor outcome. These results are derived only by additional studies with adequate sample size. CONCLUSION Our results support the use of CBT for OCD in patients with psychosis.

Variation in response to short-term antidepressant treatment between patients with continuous and non-continuous cycling bipolar disorders.

OBJECTIVES The study aimed to compare effectiveness and safety of short-term antidepressant treatment between patients with continuous (CCC) and non-continuous (N-CCC) cycling bipolar disorders. METHODS The study sample included 101 patients with bipolar disorder, 22 (21.8%) CCC and 79 (78.2%) N-CCC. Response was defined as a HDRS21 total score <7 at 12 weeks of treatment and remission as a ≥50% reduction of baseline HDRS21 total score sustained for 8 weeks. RESULTS Compared with N-CCC patients, CCC patients achieved a significantly lower percentage of response (respectively 50% vs. 82.3%, χ²=9.6, p=0.002) and remission (respectively 40.9% vs. 69.6%, χ²=6.11, p=0.013). Adjusted logistic regression analysis indicated that CCC patients were 4.3 times more likely to be non-responders and 3.3 times more likely to be non-remitters than N-CCC patients. CONCERNING AD safety, 1 (5.0%) CCC patient committed a suicide attempt and AD-emerging switch was observed in 2 patients with N-CCC (2.5%) and in 1 with CCC (4.5%). LIMITATIONS The observational nature of the study, retrospective assessment of course, and unblinded outcomes assessment. CONCLUSIONS Our findings indicate that the presence or absence of a free interval identifies two different forms of bipolar disorders with different response not only to prophylactic treatment, as previously reported, but also to short-term ADs. We submit that clinicians should take into consideration their patients׳ pattern of cycling when prescribing short-term AD treatment. Moreover, subtypes of bipolar disorders might be used as moderators of treatment response in studies assessing the efficacy or the effectiveness of antidepressant treatment.