PD Panic DisorderPanic Disorder strikes twice as many women as men and between three and six million people have experienced it. The symptoms are mostly physical with excessive worrying about the next attack in between. Some of the symptoms are:chest pains, smothering sensations, trouble breathing, weak,sweaty,dizzy, hands may tingle or feel numb, or you may even feel you may be losing your mind. The disorder can develop into phobias and into agoraphobia ..fear of going outside. The SSRI's Paxil, Zoloft, Luvox, Prozac and Celexa are often prescribed for Panic Disorder along with cognitive therapy. Xanax(alprazolam) and Clonazepam (Klonopin, Rivotril) are also prescribed.
Hum Psychopharmacol. 2004 Oct;19(7):457-65. :
The acute effects of L-theanine in comparison with alprazolam on anticipatory anxiety in humans.
Lu K, Gray MA, Oliver C, Liley DT, Harrison BJ, Bartholomeusz CF, Phan KL, Nathan PJ.
Neuropsychopharmacology Laboratory, Brain Sciences Institute, Swinburne, University of Technology, Victoria, Australia.
L-Theanine (delta-glutamylethylamide) is one of the predominant amino acids ordinarily found in green tea, and historically has been used as a relaxing agent. The current study examined the acute effects of L-theanine in comparison with a standard benzodiazepine anxiolytic, alprazolam and placebo on behavioural measures of anxiety in healthy human subjects using the model of anticipatory anxiety (AA). Sixteen healthy volunteers received alprazolam (1 mg), L-theanine (200 mg) or placebo in a double-blind placebo-controlled repeated measures design. The acute effects of alprazolam and L-theanine were assessed under a relaxed and experimentally induced anxiety condition. Subjective self-reports of anxiety including BAI, VAMS, STAI state anxiety, were obtained during both task conditions at pre- and post-drug administrations. The results showed some evidence for relaxing effects of L-theanine during the baseline condition on the tranquil-troubled subscale of the VAMS. Alprazolam did not exert any anxiolytic effects in comparison with the placebo on any of the measures during the relaxed state. Neither L-theanine nor alprazalam had any significant anxiolytic effects during the experimentally induced anxiety state. The findings suggest that while L-theanine may have some relaxing effects under resting conditions, neither L-theanine not alprazolam demonstrate any acute anxiolytic effects under conditions of increased anxiety in the AA model. 2004 John Wiley & Sons, Ltd.
J Psychiatr Res 2003 May-Jun;37(3):187-92:
Comparing anxiety disorders and anxiety-related traits in bipolar disorder and unipolar depression.
Simon NM, Smoller JW, Fava M, Sachs G, Racette SR, Perlis R, Sonawalla S, Rosenbaum JF
.
WACC 815, Massachusetts General Hospital, 15 Parkman Street, 02114, Boston, MA, USA
The frequent comorbidity of anxiety disorders and mood disorders has been documented in previous studies. However, it remains unclear whether specific anxiety traits or disorders are more closely associated with unipolar major depression (MDD) or bipolar disorder (BPD). We sought to examine whether MDD and BPD can be distinguished by their association with specific types of anxiety comorbidity. Individuals with a primary lifetime diagnosis of either bipolar disorder (N=122) or major depressive disorder (N=114) received diagnostic assessments of anxiety disorder comorbidity, and completed questionnaires assessing anxiety sensitivity and neuroticism. The differential association of these anxiety phenotypes with MDD versus BPD was examined with multivariate modeling. Panic disorder and generalized anxiety disorder (GAD) specifically emerged amongst all the anxiety disorders as significantly more common in patients with BPD than MDD. After controlling for current mood state, anxiety sensitivity and neuroticism did not differ by mood disorder type. This study supports prior research suggesting a specific panic disorder-bipolar disorder connection, and suggests GAD may also be differentially associated with BPD. Further research is needed to clarify the etiologic basis of anxiety disorder/BPD comorbidity and to optimize treatment strategies for patients with these co-occurring disorders.
Psychopharmacol Bull 2001 Spring;35(2):97-110
:
Management of treatment-refractory panic disorder.
Mathew SJ, Coplan JD, Gorman JM.
Columbia University, College of Physicians and Surgeons,
Department of Clinical
Psychobiology, New York State Psychiatric Institute, Unit 84, 1051 Riverside
Drive, New York, NY 10032, USA.
sjmatthew@hotmail.com
Treatment resistance remains a relatively common problem in panic disorder (PD)
despite the success of the selective serotonin reuptake inhibitors (SSRIs) and
cognitive behavioral therapy (CBT) as first-line agents. Factors contributing to
medication treatment resistance include inadequacy of trial duration, improper
dosage, poor tolerability, noncompliance, and medical and psychiatric comorbidity.
Poor tolerability to the SSRIs can frequently be addressed by judicious lowering
of the initial dose, with a gradual upward titration. For patients who have not
responded to one or more adequate trials of SSRIs, options include combination
treatment with a benzodiazepine or tricyclic antidepressant (TCA), augmentation
with pindolol, or switching to a different class of medication. The newer
antidepressants, particularly venlafaxine XR, seem promising as alternatives, and
might be beneficial for the refractory patient with a comorbid mood disorder.
Anticonvulsants and olanzapine might be particularly beneficial for the refractory
patient with hypomania, irritability, and insomnia, who also has demonstrated
acute SSRI hypersensitivity. Experimental therapeutics in refractory panic
probably will continue to examine the role of corticotropin releasing factor and
glutamate/GABA systems. The role of CBT in the medication refractory patient
has been explored, with preliminary suggestions of efficacy.
Discovery That Common Mood Disorders Are Inherited Together May Reveal Genetic
Underpinnings The genetic underpinnings of panic disorder and manic depressive (bipolar) illness have long eluded scientists.
Now, researchers at Johns Hopkins studying the inheritance patterns of these conditions have concluded that
they probably are not separate diseases at all, but different forms of a shared and complex biological
condition.
"We've shown that panic attacks and panic disorder are related genetically to bipolar disorder and therefore
likely share a common cause," says Dean F. MacKinnon, M.D., assistant professor of psychiatry at Hopkins and
lead author of a report on the study in the current issue of the American Journal of Psychiatry. "We still
can't say what specific gene or genes cause what, but this is a major step toward solving these problems," says
MacKinnon.
The scientists' case for a common foundation emerged from examining the disease pedigrees of 203 families
in which at least one family member had bipolar disorder. Interviews with family members led to the
identification of symptoms characteristic of major mood disorders and other psychiatric conditions in
relatives.
"We found that if one family member has both panic disorder and bipolar disorder, then the risk of panic
disorder in other relatives is greatly increased," says MacKinnon. "These links reflect the genetic complexity
of these disorders."
While genes may not tell the whole story of major psychiatric diseases, the persistent frequency in about 1
percent of the global human population, regardless of cultural or ethnic differences, and their tendency to
run in families have always pointed to a strong genetic role.
But pinning down that role is complicated by the many variations in symptoms, even within the same family.
Some, for example, have intense episodes of mania, others have mild mania, some with panic, some without.
"Gene expression is complex, and in these disorders, environmental factors and nature-nurture interactions
are all certainly involved," says MacKinnon.
Further studies of families with both panic and bipolar disorder and with bipolar disorder alone should lead to
other insights into both conditions, says MacKinnon. For instance, panic and bipolar disorder may be the same
underlying condition marked by different degrees of intensity of such symptoms as anxiety and fear, heart
palpitations, shortness of breath and dizziness. "There might be a panic flavor of bipolar disorder so that if
you have bipolar disorder, you also have panic," says MacKinnon.
Alternatively, panic vulnerability may be a fairly common trait that shows itself preferentially under certain
extreme forms of provocation, one of which is bipolar disorder.
"The exciting thing is that we can now begin to link up specific clinical features of these various disorders to a
genetic model of complex inheritance. We see that certain family members have different varieties of disease,
and now we create a model to account for this variation, and improve diagnosis and treatment," says
MacKinnon.
Other authors of the study are Peter P. Zandi, M.P.H., Jennifer Cooper, M.D., James B. Potash, M.D., M.P.H.,
Sylvia G. Simpson, M.D., M.P.H., Elliot Gershon, M.D., John Nurnberger, M.D., Ph.D., Theodore Reich, M.D., and J.
Raymond DePaulo, M.D.
The research is supported by the National Institutes of Mental Health and the NIMH Bipolar Disorder
Genetics Initiative, the Charles A. Dana Foundation Consortium on the Genetic Basis of Manic Depressive
Illness, the National Alliance for Research on Schizophrenia and Depression, and the Ted and Vada Stanley
Foundation.
Psychother Psychosom 2003 Jan-Feb;72(1):34-42
:
Increased probability of remaining in remission from panic
disorder with agoraphobia after drug treatment in patients who
received concurrent cognitive-behavioural therapy: a follow-up
study.
Biondi M, Picardi A.
Psychiatric Clinic (3rd), University of Rome 'La Sapienza', Rome, Italy.Background: Many short-term trials suggested that the combination of
psychotherapy with medication might be more effective than either treatment
alone. However, only few studies examined the long-term effectiveness of this
combination. Methods: A private practice sample of consecutive patients with
DSM-III-R panic disorder with agoraphobia who achieved remission after drug
treatment with or without concurrent cognitive-behavioural psychotherapy were
followed up. Patients were assessed before treatment, after treatment and at
each follow-up contact with the Marks-Sheehan Phobia Scale, the Hamilton
Anxiety Rating Scale, and the Hamilton Depression Rating Scale. Kaplan-Meier
survival analysis was performed on the time to panic disorder relapse. Cox
regression analysis was used to control for the possible confounding effect of
factors other than treatment. Results: Of patients who received medication alone
(n = 32), 25 (78.1%) relapsed, prevalently (65.6%) during the first year. The
estimated mean survival time was 12 months (95% CI 7-17). Of patients who
received integrated treatment (n = 21), only 3 (14.3%) relapsed. The estimated
mean survival time was 65 months (95% CI 44-86). Treatment was the only
variable associated with the occurrence of relapse, with a hazard ratio of 12.6
(95% CI 2.5-63.3) for patients who received only medication. Conclusions: Some
methodological limitations, such as treatment allocation by preference, suggest
caution in the interpretation of our results. However, the long-term therapeutic
advantage of integrated treatment over medication alone was large and
independent from known prognostic factors. The long-term effectiveness of
integrated treatment should be tested with a randomised controlled trial.
CNS Drugs 2002;16(6):425-34
:
Spotlight on paroxetine in psychiatric disorders in adults.
Wagstaff AJ, Cheer SM, Matheson AJ, Ormrod D, Goa KL.
Adis International Limited, Auckland, New Zealand.
demail@adis.co.nzParoxetine is a selective serotonin reuptake inhibitor (SSRI), with
antidepressant and anxiolytic activity. In 6- to 24-week well designed trials,
oral paroxetine 10 to 50 mg/day was significantly more effective than placebo,
at least as effective as tricyclic antidepressants (TCAs) and as effective as
other SSRIs and other antidepressants in the treatment of major depressive
disorder. Relapse or recurrence over 1 year after the initial response was
significantly lower with paroxetine 10 to 50 mg/day than with placebo and
similar to that with imipramine 50 to 275 mg/day. The efficacy of paroxetine
10 to 40 mg/day was similar to that of TCAs and fluoxetine 20 to 60 mg/day in
6- to 12-week trials in patients aged > or = 60 years with major depression.
Paroxetine 10 to 40 mg/day improved depressive symptoms to an extent similar
to that of TCAs in patients with comorbid illness, and was more effective than
placebo in the treatment of dysthymia and minor depression. Paroxetine 20 to
60 mg/day was more effective than placebo after 8 to 12 weeks' treatment of
obsessive-compulsive disorder (OCD), panic disorder, social anxiety disorder
(social phobia), generalised anxiety disorder (GAD) and post-traumatic stress
disorder (PTSD). Improvement was maintained or relapse was prevented for 24
weeks to 1 year in patients with OCD, panic disorder, social anxiety disorder or
GAD. The efficacy of paroxetine was similar to that of other SSRIs in patients
with OCD and panic disorder and similar to that of imipramine but greater than
that of 2'chlordesmethyldiazepam in patients with GAD. Paroxetine is generally
well tolerated in adults, elderly individuals and patients with comorbid illness,
with a tolerability profile similar to that of other SSRIs. The most common
adverse events with paroxetine were nausea, sexual dysfunction, somnolence,
asthenia, headache, constipation, dizziness, sweating, tremor and decreased
appetite. In conclusion, paroxetine, in common with other SSRIs, is generally
better tolerated than TCAs and is a first-line treatment option for major
depressive disorder, dysthymia or minor depression. Like other SSRIs,
paroxetine is also an appropriate first-line therapy for OCD, panic disorder,
social anxiety disorder, GAD and PTSD. Notably, paroxetine is the only SSRI
currently approved for the treatment of social anxiety disorder and GAD,
which makes it the only drug of its class indicated for all five anxiety disorders
in addition to major depressive disorder. Thus, given the high degree of
psychiatric comorbidity of depression and anxiety, paroxetine is an important
first-line option for the treatment of major depressive disorder, OCD, panic
disorder, social anxiety disorder, GAD and PTSD.
J Clin Psychopharmacol 2001 Apr;21(2):131-8
:
Absence of neuropsychologic deficits in patients receiving
long-term treatment with alprazolam-XR for panic disorder.
Gladsjo JA, Rapaport MH, McKinney R, Auerbach M, Hahn T, Rabin A,
Oliver T, Haze A, Judd LL.
Department of Psychiatry,
University of California, San Diego School of Medicine,
La Jolla 92037, USA.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.
Neuropsychopharmacology 2002 Aug;27(2):260-9
:
Effects of alprazolam on driving ability, memory functioning and
psychomotor performance: a randomized, placebo-controlled
study.
Verster JC, Volkerts ER, Verbaten MN.
Utrecht Institute for Pharmaceutical Sciences,
Department of
Psychopharmacology, University of, Utrecht, The Netherlands.
J.C.Verster@pharm.uu.nlAlprazolam is prescribed for the treatment of anxiety and panic disorder. Most
users are presumably involved in daily activities such as driving. However, the
effects of alprazolam on driving ability have never been investigated. This study
was conducted to determine the effects of alprazolam (1 mg) on driving ability,
memory and psychomotor performance. Twenty healthy volunteers participated in
a randomized, double-blind, placebo-controlled crossover study. One hour after
oral administration, subjects performed a standardized driving test on a primary
highway during normal traffic. They were instructed to drive with a constant
speed (90 km/h) while maintaining a steady lateral position within the right traffic
lane. Primary performance measures were the Standard Deviation of Lateral
Position (SDLP) and the Standard Deviation of Speed (SDS). After the driving
test, subjective driving quality, mental effort, and mental activation during driving
were assessed. A laboratory test battery was performed 2.5 h after treatment
administration, comprising the Sternberg Memory Scanning Test, a Continuous
Tracking Test, and a Divided Attention Test. Relative to placebo, alprazolam
caused serious driving impairment, as expressed by a significantly increased SDLP
(F(1,19) = 97.3, p <.0001) and SDS (F(1,19) = 30.4, p <.0001). This was confirmed by
subjective assessments showing significantly impaired driving quality (F(1,19) =
16.4, p <.001), decreased alertness (F(1,19) = 43.4, p <.0001), decreased mental
activation (F(1,19) = 5.7, p <.03) and increased mental effort during driving
(F(1,19) = 26.4, p <.0001). Furthermore, alprazolam significantly impaired
performance on the laboratory tests. In conclusion, alprazolam users must be
warned not to drive an automobile or operate potentially dangerous machinery.
Arch Gen Psychiatry 2001 Jul;58(7):681-6
:
Early coadministration of clonazepam with sertraline for panic
disorder.
Goddard AW, Brouette T, Almai A, Jetty P, Woods SW, Charney D.
Department of Psychiatry, Yale University School of Medicine, and Yale Anxiety
Clinic,
100 York St #2J, New Haven, CT 06511, USA.
andrew.goddard@yale.eduBACKGROUND: There is debate about combining benzodiazepines with selective
serotonin reuptake inhibitors in the acute treatment of panic disorder. Although
this medication combination is widely used in clinical practice, there is no
well-tested, optimal method of coadministering these medications for the
treatment of panic disorder. The purpose of this study was to test the efficacy of
early coadministration of clonazepam with sertraline in the treatment of panic
disorder. METHODS: Fifty patients with panic disorder were randomized into a
double-blind clinical trial. Patients received open-label sertraline for 12 weeks
(target dose, 100 mg/d), and in addition were randomized to groups receiving
either 0.5 mg of active clonazepam 3 times daily or placebo clonazepam for the
first 4 weeks of the trial. The clonazepam dose was then tapered during 3 weeks
and discontinued. RESULTS: Thirty-four (68%) of 50 patients completed the trial.
Drop-out rates were similar in the sertraline/placebo vs the sertraline/clonazepam
group (38% vs 25%) (P =.5). An intent-to-treat analysis (on last observation
carried forward data) revealed a much greater proportion of responders in the
sertraline/clonazepam compared with the sertraline/placebo group at the end of
week 1 of the trial (41% vs 4%) (P =.003). There was also a significant
between-group difference at the end of week 3 with 14 (63%) of 22 of the
sertraline/clonazepam group responding to treatment vs 8 (32%) of 25 of the
sertraline/placebo group (P =.05). This difference was not observed at other times
during the trial. CONCLUSION: These data indicate that rapid stabilization of
panic symptoms can be safely achieved with a sertraline/clonazepam combination,
supporting the clinical utility of this type of regimen for facilitating early
improvement of panic symptoms relative to sertraline alone.
Psychother Psychosom 2003 Jan-Feb;72(1):43-8
:
Treating medication-resistant panic disorder: predictors and
outcome of cognitive-behavior therapy in a brazilian public
hospital.
Heldt E, Manfro GG, Kipper L, Blaya C, Maltz S, Isolan L, Hirakata VN,
Otto MW.
Anxiety Disorder Program, Hospital de Clinicas de Porto Alegre,
RS and
Postgraduate Program in Medical Sciences:
Psychiatry, Universidade Federal do
Rio Grande do Sul, Porto Alegre, Brazil.Background: In Brazil, treatment of panic disorder is most frequently initiated
with pharmacotherapy, but only half of the patients can be expected to be panic
free after medication. Studies have suggested that individual or group
cognitive-behavior therapy (CBT) is an effective treatment strategy for panic
patients who have failed to respond to pharmacotherapy. Methods: Thirty-two
patients diagnosed with panic disorder with agoraphobia having residual symptoms
despite being on an adequate dose of medication were treated with 12 weeks of
group CBT. The outcome was evaluated for panic frequency and severity,
generalized anxiety, and global severity. Comorbid conditions, a childhood history
of anxiety, and defense mechanism styles were assessed as potential predictors
of treatment response. Results: Twenty-nine patients completed the 12-week
protocol. Treatment was associated with significant reductions in symptom
severity on all outcome measures (p < 0.001). Patients with depression had a poorer
outcome of the treatment (p = 0.01) as did patients using more neurotic (p =
0.002) and immature defenses (p = 0.05). Conclusion: Consistent with previous
reports, we found that CBT was effective for our sample of treatment-resistant
patients. Among these patients, depression as well as neurotic defense style was
associated with a poorer outcome. The use of CBT in Brazil for
treatment-resistant and other panic patients is encouraged.
Psychiatry Res 2002 Dec 15;113(1-2):181-92
:
Central and peripheral chemoreflexes in panic disorder.
Katzman MA, Struzik L, Vijay N, Coonerty-Femiano A, Mahamed S, Duffin
J.
Anxiety Disorders Clinic, Centre for Addiction and Mental Health-Clarke Division,
250 College Street, Toronto, M5T 1R8, Ontario, CanadaKlein (Arch Gen Psychiatry, 50, 1993, 306-317) has suggested that panic disorder
patients have a false suffocation alarm that may be associated with a lowered
threshold for carbon dioxide detection. We compared the thresholds and
sensitivities of the central and peripheral chemoreflexes between panic disorder
patients and age- and sex-matched healthy volunteers to test this aspect of the
hypothesis. We used a modified version of Read's rebreathing technique in 11 panic
disorder patients and 10 healthy volunteers to examine the peripheral and central
chemoreflex characteristics in these two populations. Subjects were examined
during three rebreathing tests: training, hyperoxic (central chemoreflex alone)
and hypoxic (combined central and peripheral chemoreflex). Panic symptoms were
retrospectively assessed between groups using a DSM-IV derived Panic Symptom
Scale. Comparisons of panic disorder patients with agoraphobia and healthy
volunteers showed no significant differences in sensitivities or thresholds. Klein's
hypothesis is not supported by these data. If a false suffocation alarm exists, its
triggering may not be implemented within the respiratory chemoreflexes.
Biol Psychiatry 2002 Nov 15;52(10):938-46
:
Anxiety sensitivity and panic disorder.
McNally RJ.
Department of Psychology,
Harvard University, Cambridge, Massachusetts 02138,
USA.Anxiety sensitivity refers to fears of anxiety-related sensations. Most often
measured by the Anxiety Sensitivity Index (ASI), anxiety sensitivity is a
dispositional variable especially elevated in people with panic disorder. Regardless
of diagnosis, ASI scores often predict panic symptoms in response to biological
challenges (e.g., carbon dioxide inhalation) that provoke feared bodily sensations.
Prospective longitudinal studies indicate that scores on the ASI predict
subsequent spontaneous attacks, indicating that elevated anxiety sensitivity is a
risk factor for panic and perhaps panic disorder. Cognitive behavioral treatment
reduces anxiety sensitivity in panic patients, perhaps protecting against relapse.
Imipramine likewise decreases anxiety sensitivity
Neurosci Lett 2002 Nov 15;333(1):41-4
:
Norepinephrine transporter gene (NET) variants in patients with
panic disorder.
Sand PG, Mori T, Godau C, Stober G, Flachenecker P, Franke P, Nothen
MM, Fritze J, Maier W, Lesch KP, Riederer P, Beckmann H, Deckert J.
Department of Psychiatry, University of Wurzburg, Fuchsleinstrazze 15,
D-97080, Wurzburg, Germany.
philipp.sand@mail.uni-wuerzburg.deSeveral lines of evidence suggest that catecholamines, especially norepinephrine,
are implicated in the etiology and/or symptomatology of panic disorder (PD). At
the cellular level, functional noradrenergic neurotransmission depends on synaptic
reuptake of norepinephrine as mediated by the norepinephrine transporter (NET).
A pharmacological target of agents with an established anti-panic efficacy, e.g.
tricyclic antidepressants, the NET is of particular interest in PD. We investigated
the NET gene for the presence of 6 naturally occurring exonic sequence variants,
5 of which give rise to amino acid substitutions (Val69Ile, Thr99Ile, Val245Ile,
Val449Ile and Gly478Ser) in a population of 87 patients with PD and 89 healthy
controls. Except for a silent substitution (G1287A), overall frequencies of variant
alleles were low (< or =0.016). None of the variants under study was found to be
associated with PD regardless of an additional diagnosis of agoraphobia.
Am Fam Physician 2002 Oct 15;66(8):1477-84
:
What to do when SSRIs fail: eight strategies for optimizing
treatment of panic disorder.
Zamorski MA, Albucher RC.
University of Michigan Medical School, Ann Arbor, USA.Selective serotonin reuptake inhibitors (SSRIs) are the drug of choice for
treatment of patients with panic disorder. Most patients have a favorable
response to SSRI therapy; however, 30 percent will not be able to tolerate these
drugs or will have an unfavorable or incomplete response. Strategies to improve
management of such patients include optimizing SSRI dosing (starting at a low
dose and slowly increasing the dose to reach the target dose) and ensuring an
adequate trial before switching to a different drug. Benzodiazepines should be
avoided but, when necessary, may be used for a short duration or may be used
long-term in patients for whom other treatments have failed. Slower-onset,
longer-acting benzodiazepines are preferred. All patients should be encouraged to
try cognitive behavior therapy. Augmentation therapy should be considered in
patients who do not have a complete response. Drugs to consider for use in
augmentation therapy include benzodiazepines, buspirone, beta blockers, tricyclic
antidepressants, and valproate sodium.
Am J Psychiatry 2002 Oct;159(10):1785-7
:
Catechol O-methyltransferase genetic polymorphism in panic
disorder.
Woo JM, Yoon KS, Yu BH.
Department of Neuropsychiatry,
Seoul Paik Hospital, Inje University, Seoul,
Korea.OBJECTIVE: The authors examined the distribution of catechol
O-methyltransferase (COMT) genotypes in patients with panic disorder as well as
the relationship between a COMT polymorphism and the clinical characteristics of
these patients. METHOD: Fifty-one patients with panic disorder and 45 healthy
comparison subjects were tested for a genetic polymorphism of COMT. Clinical
variables were assessed for the patients with panic disorder. RESULTS: The
frequency of the L/L genotype was significantly higher in the patients with panic
disorder than in the healthy subjects (19.6% versus 2.2%). Panic disorder was
significantly associated with the L allele and L/L genotype. Patients with panic
disorder who had the L/L genotype showed poorer treatment response than those
with other genotypes. CONCLUSIONS: These results suggest that the L/L
genotype of the COMT gene may be related to the development and treatment
outcome of panic disorder in some patients
Arch Gen Psychiatry 2002 Oct;59(10):905-11
:
Clinical significance of lifetime panic spectrum symptoms in the
treatment of patients with bipolar I disorder.
Frank E, Cyranowski JM, Rucci P, Shear MK, Fagiolini A, Thase ME,
Cassano GB, Grochocinski VJ, Kostelnik B, Kupfer DJ.
Department of Psychiatry, Western Psychiatric Institute and Clinic, Pittsburgh,
PA 15213, USA.
franke@msx.upmc.eduBACKGROUND: Given the observed association between panic disorder and bipolar
disorder and the potential negative influence of panic symptoms on the course of
bipolar illness, we were interested in the effects of what we have defined as
"panic spectrum" conditions on the clinical course and treatment outcome in
patients with bipolar I (BPI) disorder. We hypothesized that lifetime panic
spectrum features would be associated with higher levels of suicidal ideation and
a poorer response to acute treatment of the index mood episode in this patient
population. METHODS: A sample of 66 patients with BPI disorder completed a
self-report measure of lifetime panic-agoraphobic spectrum symptoms. Patients
falling above and below a predefined clinical threshold for panic spectrum were
compared for clinical characteristics, the presence of suicidal ideation during
acute treatment, and acute treatment response. RESULTS: Half of this outpatient
sample reported panic spectrum features above the predefined threshold. These
lifetime features were associated with more prior depressive episodes, higher
levels of depressive symptoms, and greater suicidal ideation during the
acute-treatment phase. Patients with BPI disorder who reported high lifetime
panic-agoraphobic spectrum symptom scores took 27 weeks longer than those who
reported low scores to remit with acute treatment (44 vs 17 weeks, respectively).
CONCLUSIONS: The presence of lifetime panic spectrum symptoms in this sample
of patients with BPI disorder was associated with greater levels of depression,
more suicidal ideation, and a marked (6-month) delay in time to remission with
acute treatment. Alternate treatment strategies are needed for patients with BPI
disorder who endorse lifetime panic spectrum features.
Eur Neuropsychopharmacol 2002 Oct;12(5):483-7
:
The protein kinase A in platelets from patients with panic
disorder.
Tardito D, Zanardi R, Racagni G, Manzoni T, Perez J.
Center of Neuropharmacology,
Department of Pharmacological Sciences,
University of Milan, Milan, Italy.
jperez@oh-fbf.itAlthough previous studies suggested that dysfunctions in the protein kinase A
(PKA) and in some of its substrates are associated with several psychiatric
disorders, there is no evidence regarding the possible involvement of such
components in panic disorder (PD). Thus, the aim of the present study was to
investigate the levels of PKA and Rap1 in platelets from patients with such
disorder. Twenty-four drug free patients with PD and 24 healthy volunteers
participated to the study. Employing the Western Blot analysis, immunostaining
and computer-assisted imaging, the levels of the regulatory (R, type I and type II)
and the catalytic (C) subunits of PKA, and those of Rap1 were assessed in
platelets from the two groups. The data show that patients with PD have
significantly higher levels of platelet RI and C subunits of PKA than controls,
whereas the levels of RII were unchanged. No significant differences were found
in the immunolabelling of Rap1 between groups. These findings may provide clues
toward understanding the involvement of cAMP signalling in anxiety disorders.
Expert Opin Investig Drugs 2002 Oct;11(10):1477-86
:
Escitalopram.
Burke WJ.
University of Nebraska Department of Psychiatry,
985580 Nebraska Medical
Center, Omaha, NE 68198-5580, USA.
wjburke@unmc.eduEscitalopram oxalate (S-citalopram, Lexapro), a selective serotonin re-uptake
inhibitor antidepressant which is the S-enantiomer of citalopram, is in clinical
development worldwide for the treatment of depression and anxiety disorders.
Preclinical studies demonstrate that the therapeutic activity of citalopram resides
in the S-isomer and that escitalopram binds with high affinity to the human
serotonin transporter. Conversely, R-citalopram is approximately 30-fold less
potent than escitalopram at this transporter. Escitalopram has linear
pharmacokinetics, so that plasma levels increase proportionately and predictably
with increased doses and its half-life of 27 - 32 h is consistent with once-daily
dosing. In addition, escitalopram has negligible effects on cytochrome P450
drug-metabolising enzymes in vitro, suggesting a low potential for drug-drug
interactions. The efficacy of escitalopram in patients with major depressive
disorder has been demonstrated in multiple short-term, placebo-controlled clinical
trials, three of which included citalopram as an active control, as well as in a
36-week study evaluating efficacy in the prevention of depression relapse. In
these studies, escitalopram was shown to have robust efficacy in the treatment of
depression and associated symptoms of anxiety relative to placebo. Efficacy has
also been shown in treating generalised anxiety disorder, panic disorder and social
anxiety disorder. Results also suggest that, at comparable doses, escitalopram
demonstrates clinically relevant and statistically significant superiority to placebo
treatment earlier than citalopram. Analysis of the safety database shows a low
rate of discontinuation due to adverse events, and there was no statistically
significant difference between escitalopram 10 mg/day and placebo in the
proportion of patients who discontinued treatment early because of adverse
events. The most common adverse events associated with escitalopram which
occurred at a rate greater than placebo include nausea, insomnia, ejaculation
disorder, diarrhoea, dry mouth and somnolence. Only nausea occurred in > 10% of
escitalopram-treated patients.
Hum Psychopharmacol 2002 Oct;17(7):329-33
:
The efficacy of reboxetine in the treatment-refractory patients
with panic disorder: an open label study.
Dannon PN, Iancu I, Grunhaus L.
Chaim Sheba Medical Center, Psychiatry Division, Tel Hashomer,
Affiliated with
the Sackler School of Medicine, Tel Aviv University, Israel.
dannon@attglobal.netBACKGROUND AND OBJECTIVE: Selective serotonin reuptake inhibitors (SSRIs)
are currently the first-line treatment for panic disorder, although up to 30% of
patients either do not respond to SSRIs or withdraw due to adverse events.
Reboxetine, a selective norepinephrine reuptake inhibitor (selective NRI), is
effective in treating depression and may alleviate depression-related anxiety. This
study aimed to investigate the efficacy of reboxetine in the treatment of
patients with panic disorder who did not respond to SSRIs. METHOD: In this
6-week, open-label study, 29 adult outpatients with panic disorder who had
previously failed to respond to SSRI treatment received reboxetine 2 mg/day,
titrated to a maximum of 8 mg/day over the first 10 days. Efficacy was assessed
using the Panic Self-Questionnaire (PSQ), the Hamilton Rating Scale for Anxiety
(HAM-A), the 17-item Hamilton Rating Scale for Depression (HRSD) and the
Global Assessment of Functioning (GAF) Scale. RESULTS: The 24 patients who
completed the study responded well to reboxetine treatment. Significant
improvement (p < 0.001) was observed in the number of daily panic attacks, and on
the scales measuring anxiety, depression and functioning. Reboxetine was
generally well tolerated. Five patients withdrew due to adverse events.
CONCLUSIONS: Reboxetine appears to be effective in the treatment of
SSRI-refractory panic disorder patients and warrants further clinical
investigation.
Acta Psychiatr Scand 2002 Sep;106(3):171-8
:
Relationship between perfectionism, personality disorders and
agoraphobia in patients with panic disorder.
Iketani T, Kiriike N, Stein MB, Nagao K, Nagata T, Minamikawa N, Shidao
A, Fukuhara H.
Department of Neuropsychiatry,
Osaka City University Medical School, Japan.
t-iketani@med.osaka-cu.ac.jpOBJECTIVE: In earlier reports, we found that perfectionism might be involved in
the development and/or maintenance of agoraphobia in panic disorder. The
present report extends this work by examining the relationship between
perfectionism and comorbidity with personality disorders in panic disorder
patients with agoraphobia (PDA) and those without agoraphobia (PD). METHOD:
We examined comorbidity of personality disorders by Structured Clinical
Interview for DSM-III-R Personality Disorders (SCID-II) and assessed
perfectionism using multidimensional perfectionism scale in 56 PDA and 42 PD
patients. RESULTS: The PDA group met criteria for at least one personality
disorder significantly more often than the PD group. With stepwise regression
analyses, avoidant and obsessive-compulsive personality disorders emerged as
significant indicators of perfectionism in patients with panic disorder.
CONCLUSION: These findings suggest that perfectionism in panic disorder
patients may be more common in those with comorbid personality disorders, and
may be an important target for preventive and therapeutic efforts
Acta Psychiatr Scand 2002 Sep;106(3):163-7
:
SSRIs vs. TCAs in the treatment of panic disorder: a
meta-analysis.
Bakker A, van Balkom AJ, Spinhoven P.
Sint Lucas Andreas Hospital,
Amsterdam, The Netherlands.
a.bakker@slaz.nlOBJECTIVE: To compare the short-term efficacy of selective serotonin reuptake
inhibitors (SSRIs) vs. tricyclic antidepressants (TCAs) in the treatment of panic
disorder (PD) a meta-analysis was conducted. METHOD: Included were 43 studies
(34 randomized, nine open), pertaining to 53 treatment conditions, 2367 patients
at pretest and 1804 at post-test. Outcome was measured with the proportion of
patients becoming panic-free, and with pre/post Cohen's d effect sizes,
calculated for four clinical variables: panic, agoraphobia, depression, and general
anxiety. RESULTS: There were no differences between SSRIs and TCAs on any of
the effect sizes, indicating that both groups of antidepressants are equally
effective in reducing panic symptoms, agoraphobic avoidance, depressive
symptomatology and general anxiety. Also the percentage of patients free of
panic attacks at post-test did not differ. The number of drop-outs, however, was
significantly lower in the group of patients treated with SSRIs (18%) vs. TCAs
(31%). CONCLUSION: SSRIs and TCAs are equal in efficacy in the treatment of
panic disorder, but SSRIs are tolerated better.
