Desipramine treatment in panic disorder

doi:10.1016/0165-0327(91)90003-B

Journal of Affective Disorders

Volume 21, Issue 4, April 1991, Pages 239-244

https://doi.org/10.1016/0165-0327(91)90003-B Get rights and content

Abstract

Apart from imipramine (IMI), the efficacy of tricyclic antidepressants in panic disorder (PD) has received surprisingly little investigation. The authors report on a 6 week open trial of desipramine (DMI) preceded by a 10 day placebo lead-in, in 15 patients with PD. By week 6, 80% of the patients were globally rated as much or very much improved on a mean dose of 198 mg. Much of the improvement resulted from a reduction in non-panic attack symptomatology (i.e., psychic, somatic and phobic anxiety). longer duration of illness, male gender and residual psychic anxiety were associated with poorer response in a subgroup of patients. DMI caused minimal intolerable side effects, suggesting possible compliance advantages in comparison to IMI. Beyond supporting the efficacy of DMI in PD, the results of the study point to a significant medication responsive non-panic illness component and caution against over-relying on panic attacks in assessing both illness severity and treatment response.

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BDNF-TRKB signaling system of the dorsal periaqueductal gray matter is implicated in the panicolytic-like effect of antidepressant drugs
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Citation Excerpt :
Regarding the latter drug, it is also noteworthy that its anti-escape effect in the elevated T-maze could be interpreted as a false negative, since this drug has no approved recommendation for the pharmacotherapy of panic. However, there is evidence to suggest that desipramine may indeed have beneficial effects in patients with panic disorder, although not superseding commonly used drugs such as the SSRIs (Kalus et al., 1991; Lydiard et al., 1993; Sasson et al., 1999). In conclusion, our data provide the first empirical evidence for involvement of the BDNF/TRKB signaling system in the DPAG in the panicolytic effect of ADs.
A wealth of evidence implicates the BDNF-TRKB system in the therapeutic effects of antidepressant drugs (ADs) on mood disorders. However, little is known about the involvement of this system in the panicolytic property also exerted by these compounds. In the present study we evaluated the participation of the BDNF-TRKB system of the dorsal periaqueductal gray matter (DPAG), a core structure involved in the pathophysiology of panic disorder, in AD-induced panicolytic-like effects in rats. The results showed that short- (3 days) or long-term (21 days) systemic treatment with the tricyclic ADs imipramine, clomipramine or desipramine increased BDNF levels in the DPAG. Only longterm treatment with the selective serotonin reuptake inhibitor fluoxetine was able to increase BDNF levels in this structure. After 21-day treatment, fluoxetine and the three tricyclic ADs used also increased BDNF concentration in the hippocampus, a key area implicated in their mood-related actions. Neither in the DPAG nor hippocampus did long-term treatment with the standard anxiolytics diazepam, clonazepam or buspirone affect BDNF levels. Imipramine, both after short and long-term administration, and fluoxetine under the latter regimen, raised the levels of phosphorylated TRKB in the DPAG. Short-term treatment with imipramine or BDNF microinjection inhibited escape expression in rats exposed to the elevated T maze, considered as a panicolytic-like effect. This anti-escape effect was attenuated by the intra-DPAG administration of the TRK receptor antagonist k252a. Altogether, our data suggests that facilitation of the BDNF-TRKB system in the DPAG is implicated in the panicolytic effect of ADs.
Recent advances in animal models of chronic antidepressant effects: The novelty-induced hypophagia test
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Animal models exhibiting sensitivity to chronic, but not acute, antidepressant treatment are greatly needed for studying the neural mechanisms of the antidepressant response. Although several models of acute antidepressant effects provide excellent tools for antidepressant discovery, they do not permit investigation into their therapeutic effects, which require several weeks of treatment to emerge. The inhibition of feeding produced by novelty, termed ‘hyponeophagia’, provides an anxiety-related measure that is sensitive to the effects of chronic, but not acute or subchronic, antidepressant treatment. This review evaluates the value of hyponeophagia-based tests as tools for investigating the neurobiology of the therapeutic response to antidepressant treatment. Criteria for the development and validation of animal models used to study neurobiological mechanisms of the antidepressant response are presented. Methodological considerations affecting the reliability, specificity, and ease of use of hyponeophagia-based models are also discussed. Lastly, we present a newly revised hyponeophagia paradigm, called the novelty-induced hypophagia (NIH) test, which attempts to maximize the predictive validity and practicality of the test. The NIH paradigm provides a promising new model for investigations into the neurobiology underlying the antidepressant response.
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Depression is a common disorder that impacts on all aspects of a person’s life. For the past 10 years, clinicians have focused on serotonin in their treatment of depression. This is largely due to the growing acceptance of the efficacy and safety of the selective serotonin reuptake inhibitors (SSRIs) in comparison with older tricyclic antidepressants (TCAs). However, evidence for a role of noradrenaline in depression has been accumulating for some time, beginning with the discovery that drugs which either caused or alleviated depression acted to alter noradrenaline metabolism. Until recently, the role of noradrenaline in depression was predicted from clinical experience with noradrenergic TCAs (desipramine, nortriptyline and protriptyline) and selective serotonin and noradrenaline reuptake inhibitors (venlafaxine, milnacipran). The licensing of reboxetine, a selective noradrenaline reuptake inhibitor now allows the role of noradrenaline in depression to be investigated directly. This review presents key data from the literature that support a role for noradrenaline in depression taking into account neurophysiology, psychopharmacology and clinical trial data.
Effects of lesioning noradrenergic neurones in the locus coeruleus on conditioned and unconditioned aversive behaviour in the rat
2001, Progress in Neuro-Psychopharmacology and Biological Psychiatry
- 1.
  The brain noradrenergic system may have a role in anxiety disorder. This study has examined the effect of bilateral 6-hydroxydopamine lesions of the noradrenergic neurones in the locus coeruleus (LC) of male Lister hooded rats on behaviour produced by unconditioned and conditioned aversive stimuli.
- 2.
  The 6-hydroxydopamine (4μg) lesions markedly reduced the noradrenaline content of the locus coeruleus hypothalamus, frontal cortex and the periaqueductal grey area without altering the levels of either dopamine or 5-hydroxytryptamine measured 14 days after administration.
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  Exposure to ultrasound (20 kHz at 98 dB for 60 sec), an unconditioned aversive stimulus, induced a defence response in the rats characterised by an increase in activity (running and jumping) followed by a period of inactivity (freezing).
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  These findings confirm that the locus coeruleus is involved in the regulation of fear-related behaviour in the rat both in an unconditioned and a conditioned model. Furthermore the results indicate that noradrenaline modifies defence behaviour rather than being the principle activating mechanism.
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^☆: Presented at the 142nd Annual Meeting of the American Psychiatric Association, May 7, 1989.

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Desipramine treatment in panic disorder☆

Abstract

Compr. Psychiatry

J. Affect. Disord.

Psychosomatics

Psychosomatics

Alprazolam in panic disorder and agoraphobia: results from a multicenter trial

Arch. Gen. Psychiatry

Handbook of Drug Therapy in Psychiatry

Placebo response in panic disorder

Am. J. Psychiatry

SCL-90R Manual

Clinical Psychometric Research

Effect of alprazolam and diazepam on anxiety and panic attacks in panic disorder: a controlled study

J. Clin. Psychiatry

A diagnostic interview: the Schedule for Affective Disorders and Schizophrenia

Arch. Gen. Psychiatry

Clinical and psychobiological characteristics of simultaneous panic disorder and major depression

Am. J. Psychiatry

Clomipramine treatment of agoraphobic women

Arch. Gen. Psychiatry