Mariangela Gasperini

How long should pindolol be associated with paroxetine to improve the antidepressant response

A double-blind study was undertaken to investigate the period of treatment with the beta-adrenoreceptor/5-hydroxytryptamine 1A (5-HT1A) antagonist pindolol required to enhance the antidepressant effects of paroxetine. After 1 week of a placebo run-in period, 63 untreated major depressive inpatients were randomly assigned to three different groups. Group 1 received paroxetine (20 mg/day) plus placebo (4 weeks). Group 2 received paroxetine (20 mg/day) plus pindolol (7.5 mg/day) for 1 week and placebo for 3 weeks. Group 3 received both active treatments for the entire duration of the study (4 weeks). Clinical response was defined as a reduction of the score in the Hamilton Rating Scale for Depression (HAM-D) to 8 or below. Also, to preliminarily examine whether beta-adrenoreceptor blockade was involved in the action of pindolol, another group of 10 inpatients was treated in an open-label manner with paroxetine (20 mg/day) plus 50 mg/day of the beta-adrenergic antagonist metoprolol, devoid of significant affinity for 5-HT1A receptors. At endpoint, the incidence of treatment-emergent side effects did not significantly differ among the three groups. After 1 and 2 weeks of treatment, the two groups treated with paroxetine plus pindolol displayed a significantly greater response rate than the group treated with paroxetine plus placebo. At study completion, only the patients treated with pindolol for the entire period showed a significantly greater response rate (p = 0.05). HAM-D score were also significantly lower at endpoint in patients treated with the combination for 4 weeks (p = 0.00003). The group of patients treated with paroxetine and metoprolol exhibited a side-effect profile comparable to that of paroxetine alone. Response rates were also comparable. These findings support the efficacy of pindolol, but not of metoprolol, in accelerating the antidepressant effect of paroxetine and suggest that the administration of pindolol for the entire period of the acute treatment may increase the efficacy of paroxetine.

Familial concordance of fluvoxamine response as a tool for differentiating mood disorder pedigrees

Concordance to antidepressant response in members of the same family is a common observation in clinical practice. However, few published data support this view; moreover families with affected members responder to the same antidepressant have been poorly studied. We have analyzed 45 pairs consisting of one mood disorder fluvoxamine double-responder proband and one first-degree relative with known outcome to fluvoxamine treatment. Among 45 pairs 30 (67%) were concordant for good response to fluvoxamine. In family pedigrees of concordant pairs we found a significantly higher distribution of bipolar forms in secondary cases than in families of non concordant pairs (14.9% vs 3.9% P = 0.039) suggesting that concordance to antidepressant therapy could select families with higher genetic loading.

Tryptophan hydroxylase gene and response to lithium prophylaxis in mood disorders

Lithium is an effective prophylactic agent in mood disorders but not all patients with mood disorders respond to lithium therapy; it is therefore necessary to identify responders prior to treatment. Clinical predictors account for about half of the variance and it is probable that genetic factors play a substantial role. The aim of this study was to investigate the possible association between the tryptophan hydroxylase (TPH) gene and prophylactic efficacy of lithium in mood disorders. One hundred and eight subjects affected by bipolar (n = 90) and major depressive (n = 18) disorder were followed prospectively for an average of 50.4 months and were typed for their TPH variant using polymerase chain reaction techniques. TPH variants were marginally associated with lithium outcome (F = 3.16; d.f.=2,105; P = 0.046). Subjects with the TPH*A/A variant showed a trend toward a worse response compared to both TPH*A/C and TPH*C/C variants. Consideration of possible stratification effects such as gender, polarity or age at onset did not influence the observed association. TPH variants may be a possible factor influencing the prophylactic efficacy of lithium in mood disorders.

35 % CO2 challenge in panic and mood disorders

20 patients with Panic Disorder (PD), 19 patients with Mood Disorder (MD) and 20 healthy controls inhaled one vital capacity of 35% CO2-65% O2 gas mixture and of compressed air in a double-blind, random, cross-over design. Only PD patients showed a strong reaction to 35% CO2 while MD patients and controls did not react significantly. These results support the specificity of the 35% CO2 challenge in PD patients and suggest that PD and MD are separate disorders.

A study of relapses in subjects with mood disorder on lithium treatment.

In a sample of 213 mood disorder subjects on long-term lithium treatment, we analyzed the recurrence indices of relapses during the prophylactic treatment period. The differences found in the recurrence rates were due to the current age and age of onset, duration of illness and polarity of the probands. The patients with personality disorders showed the worst relapse indices and could represent a group of mood disorder subjects with a bad outcome of lithium treatment.

A comparison between delusional and non-delusional depressives

Delusional depressive episodes may represent more sever degrees of depressive manifestations or a distinct subtype of depressive illness. To test these two alternative hypotheses, characteristics on demographic, clinical and symptomatic variables, presence of personality disorders and familial loading were compared in 57 delusional and 57 non-delusional depressive patients. The delusional group did not differ on symptomatological intensity degree, clinical and familial loading characteristics. They did differ on higher distribution of Cluster 1 personality disorders. In the delusional sample the presence of mood incongruent psychotic features and hallucinations were evaluated as possible indicators of different subtypes of delusional depression.

Clinical and demographic features of psychotic and nonpsychotic depression.

The present study evaluated clinical and demographic features of subjects with delusional versus nondelusional major depressive disorder. Two hundred eighty-eight subjects with mood disorder (bipolar disorder, n = 94; major depressive disorder, n = 194) were included in the study. No differences were observed for gender, polarity of mood disorder, age of onset, duration of index episode, number of episodes, number of previous hospital admissions, frequency of illness episodes, and number of suicide attempts. On the other hand, delusional subjects showed a higher rate of cluster A personality disorder and a lower level of education. We also detected a larger number of cluster B personality disorders among nondelusionals. Our data suggest that subjects with delusional mood disorder do not differ substantially from nondelusionals in terms of the clinical and demographic variables considered in this study except for personality disorders.