Absence of Neuropsychologic Deficits in Patients Receiving Long-Term Treatment With Alprazolam-XR for Panic Disorder

McLean Hospital, Cambridge, Massachusetts, United States
Journal of Clinical Psychopharmacology (Impact Factor: 3.24). 05/2001; 21(2):131-8. DOI: 10.1097/00004714-200104000-00003
Source: PubMed


Studies to date on the effects of benzodiazepines on neuropsychologic function have yielded conflicting data with respect to the type, severity, and duration of deficits that may be induced by these agents. As part of a placebo-controlled trial of alprazolam-XR (extended release) administered in combination with cognitive-behavioral therapy in patients with panic disorder, a battery of tests was used to measure neuropsychologic function. Thirty-eight outpatients were randomly assigned to receive either alprazolam-XR or placebo. Dosages were titrated up so that the alprazolam group (N = 18) received a mean dose of 4 mg/day (reduced in two patients because of sedative side effects). Neuropsychologic function after 6 weeks of therapy at the target dosage was compared with baseline assessments in each group. Both groups showed a statistically significant improvement from baseline to repeated assessments on measures of attention, executive functioning, psychomotor speed, and visual memory (p < 0.001); these gains were attributed to a practice effect. No significant changes were noted in measures of learning, verbal memory, or reaction time, and neither group showed any deterioration from baseline to retesting in any aspect of neuropsychologic function. These findings call into question the assumption that long-term benzodiazepine therapy produces significant neuropsychologic deficit in patients with diagnosed anxiety disorders.

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    • "Thus, the Curran (1992) and Ghoneim et al. (1983) studies suggest that memory effects may be present even among chronic BZ users. In contrast , a study by Gladsjo et al. (2001) failed to demonstrate memory deficits in a sample of chronic BZ users. Moreover, it remains to be determined whether BZassociated memory impairments are actually operative among patients with DSM- IV anxiety disorders and for information presented in psychotherapy. "
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    ABSTRACT: In laboratory studies with nonanxious participants, benzodiazepines (BZ) reliably induce anterograde amnesia. It remains unclear whether memory impairments exist for information presented in therapy among anxiety patients who are concomitantly taking BZs. This naturalistic study compared 16 panic disorder patients who were daily BZ users with 16 age- and education-matched, nonmedicated panic disorder patients. An incidental memory task assessed memory for psychoeducation material on the origins and management of somatic anxiety symptoms presented during group cognitive behavioral therapy (CBT). BZ users showed significantly poorer memory performance than controls although there were no group differences in anxiety symptoms, rates of psychiatric comorbidity, or sedation. Among BZ users, a higher number of minutes away from post peak drug-blood concentration when encoding began, was also associated with better incidental memory performance. Although causation cannot be inferred from this naturalistic study, the memory impairments observed among BZ users may contribute to the poorer efficacy of CBT previously documented in panic disorder patients receiving adjunctive BZs.
    Cognitive Therapy and Research 01/2004; 28(2):193-208. DOI:10.1023/B:COTR.0000021540.15135.45 · 1.70 Impact Factor
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    ABSTRACT: Background. Evidence of cognitive dysfunction in depressive and anxiety disorders is growing. However, the neuropsychological profile of young adults has received only little systematic investigation, although depressive and anxiety disorders are major public health problems for this age group. Available studies have typically failed to account for psychiatric comorbidity, and samples derived from population-based settings have also seldom been investigated. Burnout-related cognitive functioning has previously been investigated in only few studies, again all using clinical samples and wide age groups. Aims. Based on the information gained by conducting a comprehensive review, studies on cognitive impairment in depressive and anxiety disorders among young adults are rare. The present study examined cognitive functioning in young adults with a history of unipolar depressive or anxiety disorders in comparison to healthy peers, and associations of current burnout symptoms with cognitive functioning, in a population-based setting. The aim was also to determine whether cognitive deficits vary as a function of different disorder characteristics, such as severity, psychiatric comorbidity, age at onset, or the treatments received. Methods. Verbal and visual short-term memory, verbal long-term memory and learning, attention, psychomotor processing speed, verbal intelligence, and executive functioning were measured in a population-based sample of 21-35 year olds. Performance was compared firstly between participants with pure non-psychotic depression (n=68) and healthy peers (n=70), secondly between pure (n=69) and comorbid depression (n=57), and thirdly between participants with anxiety disorders (n=76) and healthy peers (n=71). The diagnostic procedure was based on the SCID interview. Fourthly, the associations of current burnout symptoms, measured with the Maslach Burnout Inventory General Survey, and neuropsychological test performance were investigated among working young adults (n=225). Results. Young adults with depressive or anxiety disorders, with or without psychiatric comorbidity, were not found to have major cognitive impairments when compared to healthy peers. Only mildly compromised verbal learning was found among depressed participants. Pure and comorbid depression groups did not differ in cognitive functioning, either. Among depressed participants, those who had received treatment showed more impaired verbal memory and executive functioning, and earlier onset corresponded with more impaired executive functioning. In anxiety disorders, psychotropic medication and low psychosocial functioning were associated with deficits in executive functioning, psychomotor processing speed, and visual short-term memory. Current burnout symptoms were associated with better performance in verbal working memory and verbal intelligence. However, lower examiner-rated social and occupational functioning was associated with problems in verbal attention, memory, and learning. Conclusions. Depression, anxiety disorders, or burnout symptoms may not be associated with major cognitive deficits among young adults derived from the general population. Even psychiatric comorbidity may not aggravate cognitive functioning in depressive or anxiety disorders among these young adults. However, treatment-seeking in depression was found to be associated with cognitive deficits, suggesting that these deficits relate to increased distress. Additionally, early-onset depression, found to be associated with executive dysfunction, may represent a more severe form of the disorder. In anxiety disorders, those with low symptom-related psychosocial functioning may have cognitive impairment. An association with self-reported burnout symptoms and cognitive deficits was not detected, but individuals with low social and occupational functioning may have impaired cognition. Tutkimus masennus- ja ahdistuneisuushäiriöihin liittyvistä kognitiivisista eli tiedonkäsittelyyn liittyvistä vaikeuksista on lisääntynyt viime vuosina. Tutkimus ei kuitenkaan ole ulottunut koskemaan nuoria aikuisia, vaikka masennus- ja ahdistuneisuushäiriöt ovat yleisiä tässä ikäryhmässä. Lisäksi tutkimus ei juurikaan ole koskenut ei-kliinisiä otoksia, ja psykiatrisen komorbiditeetin eli monihäiriöisyyden huomioon otto on tutkimusasetelmissa ollut heikkoa. Työuupumukseen liittyvää kognitiivista toimintakykyä on tutkittu vain muutamissa tutkimuksissa, ja niissäkin on kaikissa käytetty kliinisiä otoksia ja laajoja ikäryhmiä. Väitöstutkimuksen aluksi tehdyn kattavan kirjallisuuskatsauksen perusteella nuorten aikuisten kognitiivisia vaikeuksia masennus- ja ahdistuneisuushäiriöissä on tutkittu hyvin vähän. Siksi tämän tutkimuksen muissa osatöissä kartoitettiin väestöpohjaisessa otoksessa kognitiivista toimintakykyä yksisuuntaista masennusta ja ahdistuneisuushäiriöitä sairastaneilla nuorilla aikuisilla terveisiin verrokkeihin nähden, sekä yhteyksiä ajankohtaisten työuupumuksen oireiden ja kognitiivisten toimintojen välillä. Tutkimuksen tarkoituksena oli lisäksi selvittää, vaihteleeko kognitiivisten vaikeuksien olemassaolo sairauden piirteiden mukaan, kuten sen vakavuudesta, psykiatrisesta komorbiditeetista, tai sairastumisiästä riippuen. Tutkimuksessa mitattiin kielellistä ja visuaalista lyhytkestoista muistia, kielellistä pitkäkestoista muistia ja oppimista, tarkkaavaisuutta, toiminnanohjausta, psykomotorista prosessointinopeutta ja verbaalista yleistä älykkyyttä 21-35-vuotiaiden nuorten aikuisten väestöpohjaisessa otoksessa. Suoriutumista neuropsykologisissa testeissä verrattiin ensin puhdasta ei-psykoottista masennusta sairastaneiden ja terveiden verrokkien välillä, toiseksi puhdasta ja komorbidia masennusta sairastaneiden välillä ja kolmanneksi ahdistuneisuushäiriöitä sairastaneiden ja terveiden verrokkien välillä. Neljänneksi, ajankohtaisten työuupumuksen oireiden ja neuropsykologisen testisuoriutumisen välistä yhteyttä tarkasteltiin työssäkäyvien nuorten aikuisten kesken. Tulokset osoittivat, että masennus, ahdistuneisuushäiriö tai työuupumuksen oireet eivät olleet yhteydessä merkittäviin kognitiivisiin vaikeuksiin nuorten aikuisten väestössä, eikä edes psykiatrinen komorbiditeetti näyttänyt vaikeuttavan kognitiivista toimintakykyä näillä nuorilla aikuisilla. Hoitoon hakeutuminen masennuksessa oli yhteydessä kognitiivisiin vaikeuksiin, osoittaen, että nämä vaikeudet saattavat liittyä lisääntyneeseen yleiseen psyykkiseen pahoinvointiin. Lisäksi varhaisempi masennuksen sairastumisikä oli yhteydessä toiminnanohjauksen vaikeuksiin, mikä voi merkitä vakavampaa sairauden muotoa. Ahdistuneisuushäiriöistä kärsineillä psykotrooppinen lääkitys ja matala psykososiaalinen toimintakyky oli yhteydessä kognitiivisiin vaikeuksiin, osoittaen, että kognitiiviset vaikeudet saattavat liittyä vakavampaan sairauden muotoon. Itse arvioidut työuupumuksen oireet eivät liittyneet kognitiivisiin ongelmiin, mutta niillä, joilla on matalampi sosiaalinen ja ammatillinen toimintakyky, saattaa olla myös heikompi kognitiivinen toimintakyky.
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    ABSTRACT: In this report, recommendations for the pharmacological treatment of anxiety and obsessive-compulsive disorders are presented, based on available randomized, placebo- or comparator-controlled clinical studies. Selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment for panic disorder. Tri2-cyclic antidepressants (TCAs) are equally effective, but they are less well tolerated than the SSRIs. In treatment-resistant cases, benzodiazepines like alprazolam may be used when the patient does not have a history of dependency and tolerance. Due to possible serious side effects and interactions with other drugs and food components, the irreversible monamine oxidase inhibitor (MAOI) phenelzine should be used only when first-line drugs have failed. In generalised anxiety disorder, venlafaxine and SSRIs can be recommended, while buspirone and imipramine may be alternatives. For social phobia, SSRIs are recommended for the first line, and MAOIs, moclobemide and benzodiazepines as second line. Obsessive-compulsive disorder is best treated with SSRIs or clomipramine.
    The World Journal of Biological Psychiatry 11/2002; 3(4):171-99. DOI:10.3109/15622970209150621 · 4.18 Impact Factor
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