Four cases of panic disorder successfully treated with Kampo (Japanese herbal) medicines: Kami-shoyo-san and Hange-koboku-to
address: Naoki Mantani Department of Integrated Japanese Oriental Medicine, Faculty of Medicine, Gunma University School of Medicine, 3-39-15, Showa-machi, Maebashi, Gunma 371-8511, Japan. Email: firstname.lastname@example.org
Kampo medicines have been used to treat patients with psychogenic disorders from ancient times. In the present report the cases are described of four patients with panic disorder successfully treated with Kampo medicines. These four patients fulfilled the Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria for panic disorder with agoraphobia. The Kampo medicine Kami-shoyo-san (TJ-24) relieved panic attacks, anticipatory anxiety and agoraphobia in two patients, and Hange-koboku-to (TJ-16) relieved these symptoms in the other two patients. The patients in whom Kami-shoyo-san was effective were older and complained of more symptoms than those in whom Hange-koboku-to was effective. These Kampo medicines may be useful as additional or alternative treatments for panic disorder.
In 1980 the new diagnostic category, panic disorder, was included in Diagnostic and Statistical Manual of Mental Disorders (3rd edition; DSM-III).1 In 20% of patients with panic disorder, panic disorder follows a chronic unchangeable or waxing course despite various treatments.2 In these patients the quality of life is markedly diminished due to panic attacks, anticipatory anxiety and agoraphobia.
In the field of Kampo medicines, the treatment aims not only at improving or regaining physical health, but also to take the patient's psychic and mental imbalance into account.3 We used Kampo medicines for the treatment of panic disorder, which is accompanied by various physical and mental symptoms. In the present report we describe the cases of four patients with panic disorder who were successfully treated with the Kampo medicine Kami-shoyo-san (TJ-24) or Hange-koboku-to (TJ-16).
A 59-year-old woman visited the Department of Japanese Oriental (Kampo) Medicine (DJOM), Toyama Medical and Pharmaceutical University in March 2000 for Kampo treatment of panic disorder with agoraphobia that had persisted for 12 months despite treatment with minor tranquilizers (Table 1). Approximately 30 panic attacks occurred during 12 months, and the patient could not leave the house alone during the period from November 1999 to January 2000 because of agoraphobia. She could not take baths alone. Hange-koboku-to therapy (TJ-16, 7.5 g/day, in addition to minor tranquilizers) for 4 weeks failed to improve her attacks of choking, shortness of breath, dizziness, palpitation, nausea, numbness, chest discomfort and fear of dying. Kami-shoyo-san was therefore administered in addition to minor tranquilizers. After Kami-shoyo-san therapy (TJ-24, 7.5 g/day) for 8 weeks, the panic attacks disappeared and the patient was accordingly relieved from anticipatory anxiety thereafter. The patient became able to leave the house and take baths alone. The relief from panic disorder has continued for 9 months to date.
Table 1. Clinical data of four patients with panic disorder
|1||59||12 months||Bromazepam 6 mg, |
etizolam 1.5 mg
|2||53||10 years||Diazepam 15 mg, |
clotiazepam 5 mg,
levomepromazine 10 mg,
haloperidol 1.5 mg
|1,3,6,9,10,12||Yes||Yes|| 9 symptoms||Kami-shoyo-san||Ennen-hange-to|
|3||33||3 months||–||3,5,6,7||Yes||Yes|| 1 symptom||Hange-koboku-to||Kami-shoyo-san|
|4||45||7 years||Alprazolam 1.2 mg, |
Lorazepam 1.5 mg
|3,5,7,10,11||Yes||Yes|| 4 symptoms||Hange-koboku-to||Kami-shoyo-san|
A 53-year-old woman came to DJOM for Kampo treatment of panic disorder that had persisted for 10 years despite conventional Western therapy, which included minor or major tranquilizers and antidepressants. Ennen-hange-to (decoction) therapy (in addition to Western medicines) for 8 weeks failed to improve her attacks. Kami-shoyo-san (TJ-24, 7.5 g/day) was therefore administered in addition to Western medicines. The panic attacks, consisting of palpitation, dizziness, trembling, sweating and nausea, were reduced in frequency by 90% with Kami-shoyo-san therapy for 10 weeks, and occasional use of Kanbaku-taiso-to (TJ-72, 2.5 g) relieved the panic attacks. Discontinuation of Kami-shoyo-san for 1 month resulted in worsening of panic attacks, and readministration of Kami-shoyo-san relieved panic attacks.
A 33-year-old woman developed repeated relapses of panic attacks with choking, shortness of breath, palpitation, nausea and numbness of the fingers, accompanied by anticipatory anxiety and agoraphobia (fear of crowds). Kami-shoyo-san therapy (TJ-24, 7.5 g/day) for 4 weeks failed to improve her attacks. Her symptoms, which had persisted for 3 months, disappeared after 12 weeks of administration of Hange-koboku- to (TJ-16, 7.5 g/day), and thereafter no agoraphobic avoidance was observed. We discontinued Kampo therapy 6 months after the first visit to DJOM, and she remains well to date (for 3 years).
A 45-year-old woman came to DJOM requesting Kampo treatment for panic disorder with agoraphobia (fear of crowds), which had persisted for 7 years despite treatment with minor tranquilizers. Kami-shoyo-san therapy (TJ-24, 7.5 g/day) for 2 months failed to relieve the panic attacks, consisting of palpitation, shortness of breath, numbness, sweating and fear of dying. Hange-koboku-to was therefore administered in addition to minor tranquilizers. After 2 weeks of administration of Hange-koboku-to (TJ-16, 7.5 g/day), the panic attacks disappeared. The patient was accordingly relieved of anticipatory anxiety and no agoraphobic avoidance was observed thereafter. This patient has received Hange-koboku-to for 2 years because temporary discontinuation of Hange-koboku-to resulted in worsening of anxiety. The relief from panic disorder has continued for 2 years to date.
In all cases the diagnosis of panic disorder had been made by a psychiatrist as fulfilling the DSM-III1 or -IV4 criteria. Informed consent was obtained from all four cases before administration of Kampo medicines. During the follow-up periods, no adverse reaction attributable to Kampo medicines was observed.
The panic attacks with agoraphobia of the patients described here (except case 3) persisted over an extensive period despite treatment with several Western therapies. We were not able to determine all the therapies previously used to treat patients 2 and 4, who had suffered from panic disorder for 10 years and 7 years, respectively, before the first visit to our department. The medicines the patients received at the first visit to DJOM are listed in Table 1. The panic disorders, which other Kampo medicines failed to improve, were relieved after administration of Kami-shoyo-san (cases 1 and 2) or Hange-koboku-to (cases 3 and 4; Table 2). Thus, the alleviation of the disease may have been due to the use of Kami-shoyo-san (cases 1 and 2) or Hange-koboku-to (cases 3 and 4). In the field of Kampo medicine, both of these medicines are widely used for patients with both mental and physical symptoms.
Table 2. Herbal components of Kampo medicines
| Saiko||Bupleurum root|
| Shakuyaku||Peony root|
| Sojutsu||Atractylodes lancea rhizome|
| Toki||Angelica root|
| Sanshishi||Gardenia fruit|
| Botanpi||Moutan bark|
| Kanzo||Glycyrrhiza root|
| Shokyo||Ginger rhizome|
| Hakka||Menthol herb|
| Hange||Pinellia tuber|
| Koboku||Magnolia bark|
| Soyo||Perilla herb|
| Shokyo||Ginger rhizome|
A previous study comparing two groups characterized by the presence or absence of prominent respiratory symptoms demonstrated that the group with prominent respiratory symptoms responded better to imipramine, whereas the group without them responded better to alprazolam.5 In contrast, the symptoms of the four cases we studied (Table 1) were varied, with no apparent predominance of any of the symptoms included in the DSM criteria. Therefore, the difference of effectiveness between Kami-shoyo-san and Hange-koboku-to was not due to the presence or absence of particular symptoms included in DSM criteria.
From the viewpoint of Kampo diagnosis, patients 1 and 2, in whom Kami-shoyo-san was effective, complained of more symptoms in the standard questionnaire6 used in DJOM than patients 3 and 4. The questionnaire consists of 16 items: being easily fatigued; lingering fatigue; feeling of discomfort; lack of will power; feeling of heaviness in the whole body; feeling of heaviness in the lower body; being easily frightened; forgetfulness; irritability; restlessness; nervousness; fits of rage; inability to concentrate; easily catching the common cold; reduced sexual desire; and motion sickness. Kami-shoyo-san may be indicated for patients with multiple complaints noted in such questionnaires. The patients in whom Kami-shoyo-san was effective were older than those in whom Hange-koboku-to was effective. Other factors included in Kampo diagnosis (irritable feeling; globus hystericus (Inchu-sharen); fits of crying; sleeplessness; thirst; sweating; chest distress; feeling of heat in the upper part of the body; dizziness; and ‘abdominal Kampo diagnosis’) did not differ between the patients in whom Kami-shoyo-san was effective and those in whom Hange-koboku-to was effective.
A previous report showed that Hange-koboku- to was effective in patients with panic attack and without agoraphobia.7 Another report showed that Ryo-kei-jutsu-kan-to-go-Keishi-ka-ryukotsu-borei-to, or -go-Saiko-ka-ryukotsu-borei-to were effective for panic attack, but were ineffective for anticipatory anxiety or agoraphobia.8 In sharp contrast, Kampo medicines were effective for panic attack, anticipatory anxiety, and agoraphobia in the four cases presented here.
A central depressant effect of Magnoliae cortex (magnolia bark in English), which is contained in Hange-koboku-to, was found in an experimental study.9Magnoliae cortex contains magnolol and honokiol as its chief ingredients.10 Watanabe et al. reported that magnolol and honokiol produced central depressant effects and centrally acting muscle relaxation in experimental animals.11 The effect of Hange-koboku-to and Kami-shoyo-san on panic attack, anticipatory anxiety, and agoraphobia should be examined in experimental studies.
In conclusion, we present four cases of panic disorder that were successfully treated with Hange-koboku-to or Kami-shoyo-san. Hange-koboku-to and Kami-shoyo-san were effective against panic attack, anticipatory anxiety, and agoraphobia. Patients in whom Kami-shoyo-san was effective were older and complained of more symptoms than patients in whom Hange-koboku-to was effective. Hange-koboku-to and Kami-shoyo-san may be useful as additional or alternative treatments for panic disorder. The effectiveness of these Kampo medicines should be further examined in a larger population with panic disorder.