Acute onset of panic attacks after transdermal estrogen replacement Hagen Kunte M.D., Lutz Harms M.D., Jens Plag M.D., Rainer Hellweg M.D., Golo Kronenberg M.D. PII: DOI: Reference:
S0163-8343(14)00115-7 doi: 10.1016/j.genhosppsych.2014.05.009 GHP 6860
To appear in:
General Hospital Psychiatry
Received date: Revised date: Accepted date:
12 March 2014 9 May 2014 13 May 2014
Please cite this article as: Kunte Hagen, Harms Lutz, Plag Jens, Hellweg Rainer, Kronenberg Golo, Acute onset of panic attacks after transdermal estrogen replacement, General Hospital Psychiatry (2014), doi: 10.1016/j.genhosppsych.2014.05.009
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Minor Revision: Panic attacks after estrogen replacement Title: Acute onset of panic attacks after transdermal estrogen replacement
RI P
Hagen Kunte, MD (Author #1 and Corresponding author)
T
Running title: Panic attacks after estrogen replacement
Institution: Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin,
SC
Germany
Email: [email protected] Lutz Harms, MD (Author #2)
MA NU
Fon: +49.30.450.560275
Institution: Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin,
Jens Plag, MD (Author #3)
ED
Germany
PT
Institution: Department of Psychiatry and Psychotherapy, Charité-Universitätsmedizin Berlin, Berlin, Germany
CE
Rainer Hellweg, MD (Author #4)
AC
Institution: Department of Psychiatry and Psychotherapy, Charité-Universitätsmedizin Berlin, Berlin, Germany Golo Kronenberg, MD (Author #5) Institution: Department of Psychiatry and Psychotherapy, Charité-Universitätsmedizin Berlin, Berlin, Germany
Key words: panic attacks; panic disorder, estrogen replacement; selective serotonin reuptake inhibitors; menopausal
* The authors declare that they have no conflicts of interest related to this manuscript. 1
ACCEPTED MANUSCRIPT Abstract: Not required.
T
To the Editor,
RI P
The menopausal transition is a period of profound bodily and psychological changes. Although precise epidemiological data are scarce, the prevalence of panic disorder in perimenopausal women is estimated at around 10% [1]. Estrogen replacement
SC
therapy may offer relief from the physical symptoms of menopause. Furthermore, it may exert beneficial effects on peri- and postmenopausal psychological complaints
MA NU
[2]. However, psychiatric adverse reactions have also been reported, both in the case of treatment with female sexual hormones (e.g. for hormonal contraception, fertility treatment, perimenopausal symptoms) and the discontinuation of such treatment [35].
Here, we describe a patient who suffered from repeated panic attacks for the first
ED
time after initiation of transdermal estrogen therapy. A 47-year-old secretary presented to our emergency room after she had experienced
PT
an unexpected episode of intense anxiety three hours earlier. The attack had lasted for approximately 15 minutes. Symptoms had included shortness of breath, a racing
CE
heartbeat, a feeling of choking, trembling, dizziness and a sense of impending doom. In the morning of the same day, she had suffered a similar attack during a cab ride with friends. She also subsequently had a panic attack at the emergency room during
AC
medical workup. She reported that she had not experienced such episodes of anxiety and panic before. The patient’s medical, psychiatric and family history was unremarkable. A thorough medical evaluation including, in particular, thyroid laboratory parameters, did not reveal any significant findings. At the time of presentation, the patient was not on any medication apart from 17β-estradiol 0.6 mg/1.25 g gel twice daily. Transdermal hormone replacement had only been started three
days
previously
by
the
patient’s
gynecologist
as
a
treatment
for
perimenopausal physical symptoms, especially hot flashes and night sweats. Prior to initiation of hormone therapy, typical menopausal hormone levels had been confirmed (decrease of estradiol and anti-Müllerian hormone; increased levels of LH and FSH). The patient reported that her menstrual period had been irregular for the Minor Revision: Panic attacks after estrogen replacement
2
ACCEPTED MANUSCRIPT past 12 months. Her last period had been 3 months earlier. Upon discontinuation of estrogen replacement, panic attacks ceased almost immediately. However, menopausal complaints also re-emerged and became increasingly distressing. Four
T
months after the initial presentation, the patient was therefore started on
RI P
escitalopram 10 mg daily, which resulted in the complete and sustained remission of her symptoms.
It is relatively uncommon for panic disorder to first occur after the age of 40. Panic
SC
attacks commencing in later life require an especially careful diagnostic workup to exclude secondary causes such as medical illness, the use of certain drugs, or
MA NU
withdrawal from benzodiazepines or alcohol [6]. Estrogen replacement therapy may alleviate physical and psychological symptoms associated with menopause. However, initiation of estrogen replacement has also been linked with the development of panic attacks [3, 5]. Rapid fluctuations in estrogen levels may have a special role in the development and expression of psychiatric symptoms [5]. The
ED
transdermal route of drug administration has many advantages including bypassing hepatic first-pass metabolism and more stable drug concentrations. Although the
PT
case presented here does not definitively prove that transdermal estrogen replacement led to the manifestation of panic attacks in our patient, the sequence of
CE
events certainly seems to argue in that direction. Psychiatrists, gynecologists and general practitioners need to be aware of both the benefits and the potential psychological risks of estrogen replacement therapy. Selective serotonin reuptake
AC
inhibitors may be a useful alternative in the treatment of postmenopausal symptoms in cases when estrogen replacement would not be considered the first choice therapy.
3
ACCEPTED MANUSCRIPT Minor Revision: Panic attacks after estrogen replacement
Hickey M, Bryant C, Judd F: Evaluation and management of depressive and
RI P
1.
T
Reference
anxiety symptoms in midlife. Climacteric 2012; 15(1):3-9
Cohen LS, Soares CN, Poitras JR, Prouty J, Alexander AB, Shifren JL: Short-
SC
2.
term use of estradiol for depression in perimenopausal and postmenopausal
3.
MA NU
women: a preliminary report. Am J Psychiatry 2003; 160(8):1519-22 Dembert ML, Dinneen MP, Opsahl MS: Estrogen-induced panic disorder. Am J Psychiatry 1994; 151(8):1246 4.
Gahr M, Freudenmann RW, Connemann BJ, Kolle MA, Schonfeldt-Lecuona
ED
C: Rapid relapse in depression following initialization of oral contraception with
PT
ethinyl estradiol and chlormadinone acetate. Gen Hosp Psychiatry 2014; 36(2):230 e1-230 e2
Price WA, Heil D: Estrogen-induced panic attacks. Psychosomatics 1988;
CE
5.
AC
29(4):433-5
6. Roy-Byrne PP, Craske MG, Stein MB: Panic disorder. Lancet 2006; 368(9540):1023-32
4
S0163-8343(14)00115-7 doi: 10.1016/j.genhosppsych.2014.05.009 GHP 6860
To appear in:
General Hospital Psychiatry
Received date: Revised date: Accepted date:
12 March 2014 9 May 2014 13 May 2014
Please cite this article as: Kunte Hagen, Harms Lutz, Plag Jens, Hellweg Rainer, Kronenberg Golo, Acute onset of panic attacks after transdermal estrogen replacement, General Hospital Psychiatry (2014), doi: 10.1016/j.genhosppsych.2014.05.009
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Minor Revision: Panic attacks after estrogen replacement Title: Acute onset of panic attacks after transdermal estrogen replacement
RI P
Hagen Kunte, MD (Author #1 and Corresponding author)
T
Running title: Panic attacks after estrogen replacement
Institution: Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin,
SC
Germany
Email: [email protected] Lutz Harms, MD (Author #2)
MA NU
Fon: +49.30.450.560275
Institution: Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin,
Jens Plag, MD (Author #3)
ED
Germany
PT
Institution: Department of Psychiatry and Psychotherapy, Charité-Universitätsmedizin Berlin, Berlin, Germany
CE
Rainer Hellweg, MD (Author #4)
AC
Institution: Department of Psychiatry and Psychotherapy, Charité-Universitätsmedizin Berlin, Berlin, Germany Golo Kronenberg, MD (Author #5) Institution: Department of Psychiatry and Psychotherapy, Charité-Universitätsmedizin Berlin, Berlin, Germany
Key words: panic attacks; panic disorder, estrogen replacement; selective serotonin reuptake inhibitors; menopausal
* The authors declare that they have no conflicts of interest related to this manuscript. 1
ACCEPTED MANUSCRIPT Abstract: Not required.
T
To the Editor,
RI P
The menopausal transition is a period of profound bodily and psychological changes. Although precise epidemiological data are scarce, the prevalence of panic disorder in perimenopausal women is estimated at around 10% [1]. Estrogen replacement
SC
therapy may offer relief from the physical symptoms of menopause. Furthermore, it may exert beneficial effects on peri- and postmenopausal psychological complaints
MA NU
[2]. However, psychiatric adverse reactions have also been reported, both in the case of treatment with female sexual hormones (e.g. for hormonal contraception, fertility treatment, perimenopausal symptoms) and the discontinuation of such treatment [35].
Here, we describe a patient who suffered from repeated panic attacks for the first
ED
time after initiation of transdermal estrogen therapy. A 47-year-old secretary presented to our emergency room after she had experienced
PT
an unexpected episode of intense anxiety three hours earlier. The attack had lasted for approximately 15 minutes. Symptoms had included shortness of breath, a racing
CE
heartbeat, a feeling of choking, trembling, dizziness and a sense of impending doom. In the morning of the same day, she had suffered a similar attack during a cab ride with friends. She also subsequently had a panic attack at the emergency room during
AC
medical workup. She reported that she had not experienced such episodes of anxiety and panic before. The patient’s medical, psychiatric and family history was unremarkable. A thorough medical evaluation including, in particular, thyroid laboratory parameters, did not reveal any significant findings. At the time of presentation, the patient was not on any medication apart from 17β-estradiol 0.6 mg/1.25 g gel twice daily. Transdermal hormone replacement had only been started three
days
previously
by
the
patient’s
gynecologist
as
a
treatment
for
perimenopausal physical symptoms, especially hot flashes and night sweats. Prior to initiation of hormone therapy, typical menopausal hormone levels had been confirmed (decrease of estradiol and anti-Müllerian hormone; increased levels of LH and FSH). The patient reported that her menstrual period had been irregular for the Minor Revision: Panic attacks after estrogen replacement
2
ACCEPTED MANUSCRIPT past 12 months. Her last period had been 3 months earlier. Upon discontinuation of estrogen replacement, panic attacks ceased almost immediately. However, menopausal complaints also re-emerged and became increasingly distressing. Four
T
months after the initial presentation, the patient was therefore started on
RI P
escitalopram 10 mg daily, which resulted in the complete and sustained remission of her symptoms.
It is relatively uncommon for panic disorder to first occur after the age of 40. Panic
SC
attacks commencing in later life require an especially careful diagnostic workup to exclude secondary causes such as medical illness, the use of certain drugs, or
MA NU
withdrawal from benzodiazepines or alcohol [6]. Estrogen replacement therapy may alleviate physical and psychological symptoms associated with menopause. However, initiation of estrogen replacement has also been linked with the development of panic attacks [3, 5]. Rapid fluctuations in estrogen levels may have a special role in the development and expression of psychiatric symptoms [5]. The
ED
transdermal route of drug administration has many advantages including bypassing hepatic first-pass metabolism and more stable drug concentrations. Although the
PT
case presented here does not definitively prove that transdermal estrogen replacement led to the manifestation of panic attacks in our patient, the sequence of
CE
events certainly seems to argue in that direction. Psychiatrists, gynecologists and general practitioners need to be aware of both the benefits and the potential psychological risks of estrogen replacement therapy. Selective serotonin reuptake
AC
inhibitors may be a useful alternative in the treatment of postmenopausal symptoms in cases when estrogen replacement would not be considered the first choice therapy.
3
ACCEPTED MANUSCRIPT Minor Revision: Panic attacks after estrogen replacement
Hickey M, Bryant C, Judd F: Evaluation and management of depressive and
RI P
1.
T
Reference
anxiety symptoms in midlife. Climacteric 2012; 15(1):3-9
Cohen LS, Soares CN, Poitras JR, Prouty J, Alexander AB, Shifren JL: Short-
SC
2.
term use of estradiol for depression in perimenopausal and postmenopausal
3.
MA NU
women: a preliminary report. Am J Psychiatry 2003; 160(8):1519-22 Dembert ML, Dinneen MP, Opsahl MS: Estrogen-induced panic disorder. Am J Psychiatry 1994; 151(8):1246 4.
Gahr M, Freudenmann RW, Connemann BJ, Kolle MA, Schonfeldt-Lecuona
ED
C: Rapid relapse in depression following initialization of oral contraception with
PT
ethinyl estradiol and chlormadinone acetate. Gen Hosp Psychiatry 2014; 36(2):230 e1-230 e2
Price WA, Heil D: Estrogen-induced panic attacks. Psychosomatics 1988;
CE
5.
AC
29(4):433-5
6. Roy-Byrne PP, Craske MG, Stein MB: Panic disorder. Lancet 2006; 368(9540):1023-32
4
