WO2014128882A1

WO2014128882A1 - Therapeutic agent for anxiety depression

Info

Publication number: WO2014128882A1
Application number: PCT/JP2013/054344
Authority: WO
Inventors: 久宣貝谷
Original assignee: 医療法人和楽会
Priority date: 2013-02-21
Filing date: 2013-02-21
Publication date: 2014-08-28
Also published as: JPWO2014128882A1

Abstract

A medicine that comprises a compound, or a pharmaceutically acceptable salt thereof, for treating depression accompanied by intrusive cognitive emotion, i.e., so-called anxiety depression, said compound having an anti-noradrenaline effect, anti-dopamine effect, anti-serotonin receptor 2 effect and serotonin 1A receptor partial agonist effect. According to the present invention, a medicine, which comprises a spirone compound, in particular perospirone, or a pharmaceutically acceptable salt thereof for treating depression accompanied by intrusive cognitive emotion, more particularly, for treating depression by preventing depressive-anxious paroxysmal to ameliorate depression, can be provided.

Description

Drugs for anxiety depression

The present invention relates to a medicament for the treatment of depression with invasive cognitive emotion, so-called anxiety depression, which has an anti-noradrenaline action, an anti-dopamine action, an anti-serotonin receptor 2 action and a serotonin 1A receptor partial agonist action. .

Atypical Depression (AD) or posttraumatic stress disorder (Posttraumatic
Concerning mental disorders such as Stress Disorder (PTSD), its cause and drug treatment have been discussed. However, there are many unclear points about the cause, and the drug treatment has not been established due to this fact.

Atypical depression is also called a new type of depression and is a type of depression that has been called "neurotic depression". Depression often seen in women, also called `` weather shop depression '', although it continues to be depressed more, but if there are good things and fun events, the previous malfunctions like a lie quickly and well Become. However, it does not last long and is characterized by returning to a depressed mood. Furthermore, it is a disease that shows the opposite characteristics of conventional "depression", such as running overeating, gaining weight, and sleeping as much as possible.

Post-traumatic stress disorder is a disease that causes a variety of stress disorders caused by shocking wounds on the heart that occur after an event that can be fatal or severe.

Conventionally, diagnostic criteria for atypical depression include mood responsiveness, hypersomnia, overeating (weight gain), lead-like paralysis, and rejection hypersensitivity. In particular, rejection hypersensitivity is a core symptom of AD and mood responsiveness is It has been a necessary condition.

It is known that rejection hypersensitivity appears in avoidable personality disorder and social anxiety disorder (SAD). This rejection hypersensitivity is also known to appear in phobia, panic disorder and self-loving personality through stress in human relationships. There is a hypothesis that atypical depression is triggered by this rejection hypersensitivity, particularly interpersonal hypersensitivity (see Non-Patent Document 1).

It is known that symptoms such as flashback, anxiety / fear, and depression appear in post-traumatic stress disorder. Since flashback, which is a core symptom of post-traumatic stress disorder, also appears in atypical depression, there is also a hypothesis that atypical depression is a mild post-traumatic stress disorder (see Non-Patent Document 1). ).

On the other hand, from the observation of depression accompanied by panic disorder (PD) and social anxiety disorder (SAD), anxiety-depressive mixed symptoms (intrusive cognitive emotion) as independent disease, that is, anxiety / depressive seizure (Depressive- anxious paroxysmal (DAP) is presumed (Non-patent Document 1). This anxiety / depressive attack is considered to be an important target symptom that develops from anxiety disorder to mood disorder, and is known to appear in social anxiety disorder, panic disorder, and atypical depression that tend to occur together. Although the clinical significance of anxiety / depressive attacks has not been clarified, the present inventor proposes that anxiety / depressive attacks are important symptoms that have been overlooked in the above mental disorders (non-patented). Reference 2).

The present inventor has submitted a hypothesis of occurrence of atypical depression based on the above background and clinical experience (Non-patent Document 1). In other words, anxiety disorders (phobia, panic disorder, social anxiety disorder) gain "rejection sensitivity" through stress in human relationships, and are mildly injured as a mood disorder "traumatic stress disorder" “Atypical depression” develops and symptoms including “anxiety / depressive attack” appear (see FIG. 1).

However, there are still many unclear points about the etiology of mental illnesses such as atypical depression and post-traumatic stress disorder, and due to this, there is a problem that there is no drug that can accurately treat these diseases. there were.

The present inventor has set a hypothesis that the three major signs of atypical depression are rejection hypersensitivity, PTSD symptoms (flashback), and anxiety / depressive seizures based on the above background and further clinical experience. . Furthermore, based on this hypothesis, the present inventor has previously focused clinically on the fact that a compound that suppresses the three major signs of atypical depression, particularly perospirone, has an effect on atypical depression and PTSD symptoms. It was found in his own clinical experience that the above-mentioned diseases having anxiety / depressive seizures (intrusive cognitive emotions) were not found in his own clinical experience, and the present invention was completed.

In order to achieve the above object, the medicament according to the present invention is as follows. That is,
[1]
A medicament for the treatment of depression having an invasive cognitive emotion, which has an anti-noradrenaline action, an anti-dopamine action, an anti-serotonin receptor 2 action and a serotonin 1A receptor partial agonist action.
[2]
The medicament according to [1], wherein the depression having an invasive cognitive emotion is either atypical depression or post-traumatic stress disorder.
[3]
The medicament according to [1] or [2], wherein the depression having an intrusive cognitive emotion is atypical depression.
[4]
The medicament according to any one of [1] to [3], wherein the depression having an invasive cognitive emotion is a depression having an invasive cognitive emotion accompanied by panic disorder or social anxiety disorder.
[5]
The medicine according to any one of [1] to [4], which improves depression by suppressing anxiety / depressive attacks.
[6]
Any one of [1] to [5], wherein the medicament for treating depression having an invasive cognitive emotion contains at least one compound selected from the group consisting of perospirone and lurasidone as an active ingredient. The pharmaceutical according to Item.
[7]
The medicament according to any one of [1] to [6], wherein the medicament for treating depression having an invasive cognitive emotion contains perospirone as an active ingredient.
[8]
The medicine according to [6] or [7], wherein the active ingredient is taken in a daily dose of 4 mg to 48 mg.
[9]
The combination medicine according to any one of [1] to [8], further comprising an additional drug for reducing akathisia, which is a side effect of the medicine.
[10]
The combined medicine according to [9], wherein the additional drug is an anticholinergic or benzodiazepine psychiatric drug.
[11]
The combination medicine according to any one of [1] to [10], further comprising components of an excipient, a binder, and a lubricant.
[12]
The medicament according to [11], wherein the administration form is a tablet.
[13]
Depression with invasive cognitive emotion of a composition comprising a compound or a pharmaceutically acceptable salt thereof, which has an anti-noradrenaline action, an anti-dopamine action, an anti-serotonin receptor 2 action and a serotonin 1A receptor partial agonist action Use as a therapeutic drug.

According to the present invention, it is possible to provide a pharmaceutical comprising a specific compound for treating depression having an invasive cognitive emotion, particularly perospirone or a pharmaceutically acceptable salt thereof.

It is a figure which shows the generation | occurrence | production mechanism hypothesis of the atypical depression described by this invention. It is a figure which shows the improvement state after 10 weeks in one patient treated with the pharmaceutical concerning this invention.

Hereinafter, embodiments of the present invention will be described in detail.

The medicament according to the present invention has an anti-noradrenaline action, an anti-dopamine action, an anti-serotonin receptor 2 action and a serotonin 1A receptor partial agonist action, and has depression with invasive cognitive emotion, so-called anxiety depression, for treatment Or a pharmaceutically acceptable salt thereof.

In the present invention, “depression with invasive cognitive emotion” is defined as depression having anxiety / depressive attacks as clinical symptoms, and is also referred to as anxiety depression. For anxiety depression, typical disease (Atypical depression)
Depression (AD) (also called “new depression”) and posttraumatic stress disorder
Disorder: PTSD) is included. These depressions are known to frequently accompany panic disorder or social anxiety disorder.

The present inventor has proposed the hypothesis that the three major signs of atypical depression are rejection hypersensitivity, PTSD symptoms (especially flashback), and anxiety / depressive seizures based on the above circumstances and further own clinical experience. (See Non-Patent Document 1). In this hypothesis, anxiety disorders (phobia, panic disorder, social anxiety disorder) acquired "rejection sensitivity" through stress in human relations, and minor injury as a mood disorder "traumatic stress disorder" failure It is said that atypical “atypical depression” develops and symptoms including “anxiety / depressive attack” appear (see FIG. 1).

It has been suggested that each of the three major signs of atypical depression may have its own blocking agent. The blocking agent for rejection hypersensitivity is a dopamine receptor 2 blocking agent (hereinafter also referred to as “D2 blocking agent”), and the blocking agent for PTSD symptoms is also referred to as a serotonin receptor blocking agent (hereinafter referred to as “5HT blocking agent”). ), A dopamine blocker and a noradrenaline blocker, and the anxiety / depressive seizure blocker is a dopamine blocker and a noradrenaline blocker (hereinafter also referred to as “NA blocker”), as indicated below. Has been.

The D2 blocker is a drug that blocks dopamine (hereinafter also referred to as “DA”) 2 receptor, and it is known that there are two classes of D2 receptor, D2S and D2L. The 5HT blocker is a serotonin receptor blocker, and is classified into 11 types including 5HT1 to 5HT7. The NA blocker is an adrenergic receptor blocker, and two classes of α and β types are known.

Ponusamy et al. (2005) reported that systemic administration of D2 blockers promotes conditioned fear extinction learning (Ponnusamy R, Nissim HA, Barad M. Systemic blockade of D2-like dopamine receptors facilitates extinction
Learn Mem. 2005 Jul-Aug; 12 (4): 399-406.). There is also an idea that atypical depression and PTSD can be regarded as a fear-conditioned state for trauma and minitrauma. In addition, it has been confirmed in animals that increased dopamine activity in the prefrontal cortex promotes elimination learning. From these points, it is possible that rejection hypersensitivity is suppressed by an anti-dopaminergic action such as a D2 blocking action or a DA increasing action in the prefrontal cortex.

* Reports on the effects of use of psychiatric drugs targeting the basic symptoms of PTSD are very limited. However, you can refer to reports that mention the effects of PTSD on basic symptoms as follows.

According to Baker et al. (2009), risperidone was used for supplementary use, although the number of cases was small and the basic symptoms of PTSD were not targeted (Baker DG, Nievergelt). CM, Risbrough VB. Post-traumatic stress disorder: emerging
Concept of pharmacotherapy. Expert Opin Emerg Drugs. 2009 Jun; 14 (2): 251-72).

Ahern et al. (2011) reported that risperidone and quetiapine had a reduced score of invasion and hyperalgesia and had limited effects on PTSD (Ahearn EP, Juergens T, Cordes T, Becker). T, Krahn D. A review of atypical
antipsychotic medications for posttraumatic stress disorder. Int Clin Psychopharmacol.
2011 Jul; 26 (4): 193-200.).

Also, according to Richardson et al. (2011), in a study retrospectively studied with aripiprazole treatment for 12 weeks, the Beck Depression Inventory score was reduced from 30.44 to 20.67, and the score decreased by more than 20% Of 10 out of 27 (37%) reported that PTSD had an effect on depression (Richardson JD, Fikretoglu D, Liu A, McIntosh D. Aripiprazole
augmentation in the treatment of military-related PTSD with major depression: a
retrospective chart review. BMC Psychiatry. 2011 May 17; 11: 86).

Risperidone, quetiapine, and aripiprazole, which have been reported to have limited effects on PTSD, are all blockers of D2 and 5HT1A receptors, although to varying degrees. Therefore, it was considered that the basic symptom of PTSD may be suppressed by the serotonin receptor 1A partial agonistic action by an antagonist of 5HT1A receptor. Meyer et al. (2003) also reported that increased 5-HT2 receptors were observed in depression (Meyer JH, McMain S, Kennedy SH, Korman L, Brown GM, DaSilva JN, et al. Dysfunctional Attitudes and 5-HT2
Receptors During Depression and Self-Harm. Am J Psychiatry 2003; 160: 90-99). 5-HT2 receptors may be associated with depressive symptoms such as in PTSD and AD.

Suzuki et al. (2011) reported that an adrenal medullary tumor, which was diagnosed by an increase in blood noradrenaline levels, had anxiety / depressive attack and disappeared completely after tumor removal (Suzuki M, Konno C, Takahashi S, Uchiyama M. Hidden harm.
Lancet 2011; 377: 874). In this respect, there is a possibility that anxiety / depressive attacks can be suppressed by an anti-noradrenaline action by NA blockers.

In view of the above, a drug having both anti-dopaminergic action, 5-HT receptor action (particularly anti-serotonin receptor 2 action and serotonin 1A receptor partial agonist action), and anti-noradrenaline action has the above-mentioned atypical depression. The possibility of suppressing the three major signs was considered.

Psychotropic drugs indicated for several schizophrenia have all of these anti-dopaminergic effects, 5-HT receptor action (especially anti-serotonin receptor 2 action and serotonin 1A receptor partial agonist action) and anti-noradrenaline action. The possibility of having an effect was considered.

Perospirone has been used as a therapeutic agent for schizophrenia and has a strong affinity for the D2 receptor, and has the effect of increasing free dopamine (DA) in the prefrontal cortex in addition to its direct effect on the receptor. In a rat brain perfusion experiment, perospirone has been reported to increase DA in the prefrontal cortex approximately 2-fold (Mitsuaki Murasaki et al., Clinical Psychopharmacology, Vol. 11, No. 5, 845-854, 2008). .

In addition, perospirone has a strong affinity for the 5HT2 receptor and the 5HT1 receptor. Drevets et al. (2008) report a decrease in 5-HT1 receptors in depression (Drevets et
al .; Nucl Med Biol. 2007 Oct; 34 (7): 865-77). Nash et al. (2008) also reported a decrease in 5-HT1 receptors in panic disorders. In addition, Lanzenberger et al. (2007) reported a decrease in 5-HT1 receptors in social anxiety disorder (Lanzenberger RR et al .; Biol Psychiatry. 2007 May 1; 61 (9):
1081-9). From these points, it is considered that the 5HT receptor 1A partial antagonism of perospirone has a therapeutic effect on these mental disorders.

Furthermore, Ishibashi and Ohno (2004) have reported that perospirone is not as good as risperidone, but also has an α1 receptor blocking action (Mitsuaki Murasaki et al., Clinical Psychopharmacology, Vol. 11, No. 5, 845-). 854, 2008).

It has been reported that the binding affinity Ki of perospirone for the D2 receptor, 5HT2 receptor, 5HT1A receptor and α1 receptor is 0.874, 0.252, 2.21 and 0.132 nM, respectively. (Mitsuaki Murazaki et al., Clinical Psychopharmacology, Vol. 11, No. 5, pp. 845-854, 2008). Due to these binding affinities Ki, perospirone is antagonistic to D2 receptor, 5HT2 receptor, 5HT1A receptor and α1 receptor, compared to risperidone, quetiapine, aripyrazole, olanzapine, etc., which are conventional drugs for various mental disorders As a result, it turned out to be all good.

Similar to perospirone, compounds that can suppress the three major symptoms of atypical depression include serotonin-dopamine antagonists such as lurasidone (Ishiobashi et al., The Journal of Pharmacology and Experimantal
Therapeutics, Vol. 334, No. 1, 2010). The general names of these compounds are as follows:

Perospirone: cis-N- [4- [4- (1,2-benzisothiazol-3-yl) -1-piperazinyl] butyl] cyclohexane-1,2-dicarboxamide and lurasidone: (3aR, 4S, 7R, 7aS) -2-{(1R, 2R) -2- [4- (1,2-benzisothiazol-3-yl) piperazin-1-ylmethyl] cyclohexylmethyl} hexahydro-4,7-methano-2H -Isoindole-1,3-dione.

The chemical structures of the above compounds are shown below. For perospirone, the chemical structural formula of perospirone hydrochloride dihydrate contained in 4 mg of commercially available Luran (registered trademark) tablets and the like is shown. As for lurasidone, lurasidone hydrochloride contained in Latuda tablets is shown.

Perospirone hydrochloride dihydrate

Lurasidone hydrochloride

The perospirone hydrochloride dihydrate and lurasidone hydrochloride can be produced by a known production method. A preparation containing a tablet containing at least one of these compounds as an active ingredient can also be produced by a known method. For example, perospirone is disclosed by Ono et al. (2001) (Sumitomo Chemical 2001-I, pp. 38-45).

Therefore, perospirone among the above compounds was applied to depression with invasive cognitive emotion. The effects were examined at the Nagoya Mental Clinic (1-16 Sakaimachi, Nakamura-ku, Nagoya, Imon Nagoya Building 6F) and Akasaka Clinic (3-9-18 Akasaka, Minato-ku, Tokyo BIC Akasaka Building 6F).

The following CGI-I (Clinical global impression-improvement scale) was used for 32 subject cases (24 women, 8 men; age 17-68 years; daily dose 4-48 mg) Evaluation was based on the overall clinical improvement.

As shown in the table below, the evaluation results showed improvement in all patients with prominent improvement 59%, moderate improvement 34%, and mild improvement 6%. Therefore, it was found that the perospirone preparation according to the present invention is highly effective in cases with anxiety / depressive attacks.

As described above, in most patients, anxiety / depressive seizures disappeared and the depression was relieved. On the other hand, patients who had an anxiety / depressive attack for more than 10 years lost their anxiety / depressive attack, but it took time to improve their depression. Since these therapeutic effects can be confirmed even in the case where perospirone alone is administered without a concomitant drug, it is certain that it is not due to the effect of the concomitantly administered drug but perospirone.

Three of the above cases (case 1: patient SC, 56 years old, housewife, case 2, patient TM, 26 year old female, former hospitality and case 3, patient OS, 38 year old male, unemployed) are described in detail in the examples. Describe.

From the above, in depression patients with intrusive cognitive emotions, perospirone was able to eliminate anxiety / depressive seizures and improve depression through disappearance of anxiety / depressive seizures. Many patients who have anxiety / depressive seizures such as atypical depression (new type of depression) and PTSD are useful for treatment of diseases in these patients.

Of the side effects of the above compounds, such as perospirone, Akathisia is an unpleasant side effect that Mumuzu and Soisova are not standing still, and insomnia occurs at night.

The medicament according to the present invention further includes a psychiatric drug such as an anticholinergic antiparkinsonian or a benzodiazepine minor tranquilizer, or can be used in combination with these psychiatric drugs. By further including or concomitantly using these psychiatric drugs, akathisia, which is a side effect of the spirone compound, can be reduced.

As the anticholinergic antiparkinsonian agent, Tasmoline (registered trademark) tablets (generic name: biperiden hydrochloride) and tremin (registered trademark) tablets (generic name: trihexyphenidyl hydrochloride) can be used. From this point, Tasmoline (registered trademark) tablets (generic name: biperidene hydrochloride) are preferable. Examples of the benzodiazepine-based minor tranquilizer include Wipacs (registered trademark) tablets (generic name: lorazepam), Solanax (registered trademark) tablets (generic name: alprazolam), among others, Waipacs (registered trademark) from the viewpoint of immediate effect. ) Tablets (generic name: lorazepam) are preferred.

The medicament according to the present invention further contains components such as excipients, binders and lubricants in addition to the above compound, the anticholinergic antiparkinson agent and / or the benzodiazepine minor tranquilizer to be blended. It can be set as a pharmaceutical composition.

The medicament according to the present invention may contain 4 mg to 60 mg of the above compound as a daily dose. When blended as described above, biperidene hydrochloride can contain 3 mg to 6 mg daily and lorazepam can contain 1.5 mg to 3 mg daily.

Such a pharmaceutical composition can take various administration routes such as oral preparations, transdermal preparations, and external preparations. In addition, the pharmaceutical composition can take various dosage forms such as tablets, capsules, injections, etc., but tablets are preferred from the viewpoint of patient QOL.

The use as a medicament according to the present invention is a use of a medicament containing the above compound or a pharmaceutically acceptable salt thereof for the treatment of depression having an invasive cognitive emotion.

Case 1: Patient SC, 56 years old, housewife (chief complaint) has a strong feeling of fatigue, cannot do housework at all, self-care is almost impossible, and somehow lives with the assistance of her husband.
(Patient history) 3-4 years old: Insect / fear of injection, hand-washing compulsion, but friendly and friendly. Before and after entering elementary school; I heard my father's grandmother who was hostile to her mother telling her uncle to his uncle. I thought that the mother who was bullied by her grandmother seemed sorry for her childhood. He often suffered physical violence during his school days from his father. Elementary school 2nd-5th graders were often abused and bullied. Anxiety / depressive seizures occurred for the first time while traveling abroad with a husband 16 years ago (40 years old). He even made a surprising scream. Later, lead-like paralysis and interpersonal hypersensitivity were prominent, and there have been four wrist cuts to date. I often felt sick and dropped off on a crowded train. Fourteen years ago, around the age of 42, the motivation and tiredness that made it impossible to shop in the neighborhood appeared, and she continued to live in a chair all day. Since then, he has been to 5 clinics but has not improved. The situation continues and bathing is done twice a month and all housework is the husband's job. There was severe anxiety / depressive seizure one week before the first visit, and the body became stiff. Currently, anxiety / depressive attacks are 4-5 times a month. At that time, a scene where the grandmother spoke badly at an early age flashed back. She hates her eyes at the first visit and wears sunglasses and visits her husband.
(Diagnosis) Diagnosis: History of specific phobia, social anxiety disorder, agoraphobia, atypical depression failure type, anxiety / depressive attack 1-3 / month, CGI-S: 7.
(Prescription and progress) Three tablets of Luran (4 mg), three tablets of Tasmoline (1 mg), and three tablets of Wipac (0.5 mg) were administered at a minute of 3 after each meal. Eleven days after the first visit, there were no anxiety / depressive attacks. Visit without sunglasses. Bathing three times a week. I went to the beauty salon where I did laundry. I didn't feel like getting up. Awakened because the sleep-inducing agent that had been prescribed until then disappeared. Akathisia appeared. CGI-S: 5. Luran (4 mg) 3 tablets → 4 tablets, tasmorine 3 mg → 6 mg, Wipacs tablets 1.5 mg → 3 mg. Levotomin tablet 10 mg, Halcyon tablet 0.25 mg, and Rohypnol tablet 2 mg were added. 18 days after the first visit, a telephone revisit was carried out, and due to dizziness, Lulan 4 tablets → 3 tablets, and levotomin was discontinued. 21 days after the first visit, there was one anxiety / depressive attack, but it disappeared immediately. Daily function decreased slightly due to side effects. CGI-S: 6. 69 days after the first visit, cooking is over half. There are still days when I feel bad, but overall it is good. Anxiety / depressive attacks completely disappeared. CGI-S: 4.
(Diagnosis 10 weeks after the first visit) Psychological examination and CGI-S revealed that the symptoms were greatly improved. CGI-S improved from 7 to 4, and CGI-1 improved greatly. The psychological test and CGI-S after 10 weeks are shown in FIG.

Case 2, Patient TM, 26-year-old female, former hospitality (patient history) father of machinist, mother and older sister family. Excessive anxiety disorder from elementary school, selective silence from second grader to second grader, social anxiety disorder becoming high school student. I can't forget that I was ignored by a friend at the elementary school or written badly at a desk. When I was in my second year of high school, I didn't get into the circle of friends and sometimes I was absent from school. Soon after graduating from medical school at the age of 18 and getting a job (22 years old), a severe panic attack appeared and was delayed. Later, anxiety / depressive attacks began to occur frequently, and repeated severe wrist cuts. Half a year before the visit, I was unable to work due to anxiety / depressive seizures, general malaise, and decreased motivation. When an innocent phone call was received from his mother or sister, he reacted violently. When I thought I could get the money I worked hard, I got angry and made a cruel wrist cut. The doctor who treated the wound reported that he was at risk of suicide and was protected. He refused to visit the hospital because he was unable to see a patient who would make a wrist cut. At the time of the first visit, he hides his face with a large mask and enters the room. Lamenting the state of unsupported loneliness, he tries to show his wrist cuts as bad. Countless large scars were seen from the wrist to the upper left arm. Panic attacks are not prominent at present, but there are several anxiety / depressive attacks every day, and the desire for wrist cuts is constant. I have collected my wrist cut photos for the past year. If you look at the blood in the photo, you can put up with the wrist cut.
(Diagnosis) Psychological examination: Square fear scale; 65/100 (altitude), social anxiety disorder scale; 131 (highest degree), Leibovitz social anxiety disorder scale; 94 (highest degree), University of Tokyo egogram; wall flower ( Panic), panic disorder questionnaire; recent panic attacks 15 symptoms, anticipation anxiety moderate. Diagnosis of social anxiety disorder, panic disorder, unspecified depression disorder, avoidance and addiction personality disorder.
(Prescription and progress) Luran 8mg 1 tablet after dinner, Tasmoline (1mg) 3 tablets 3. After 1 week, the frequency of anxiety / depressive seizures did not change, but the intensity of the content slightly decreased. I could afford to call my father sick. Luran 8mg 2 tablets 2 parts, Tasmoline (1mg) 3 tablets part 3. After 2 weeks, anxiety / depressive attacks have not decreased, but duration has been shortened. I was able to put up with a craving for Liskat. I was able to go out with my friend. Akathisia appears. Luran 4mg 3 tablets 3 parts, Wipacs (0.5mg) 3 tablets part 3. After 3 weeks, the anxiety / depressive attack disappeared. However, vague anxiety and sadness remain. I went shopping at night. I also talked to others. Luran 4mg 3 tablets 3 tablets, Wipacs (0.5mg) 3 tablets 3. 3. After 4 weeks, there was no anxiety / depressive attack. Take a shower after 1 hour walk every morning as instructed. I didn't feel like making a wrist cut.
(Changes in psychological examination findings from the first visit to 4 weeks) Beck Depression Inventory 56 → 35, Self-Describing Depression Scale 67 → 50, Anxiety Depression Scale 61 → 51, Clinical General Impression Scale Severity 7 (most severe) Pathological symptoms) → 4 (moderate pathological symptoms), (clinical improvement of general impression scale 1 (prominently improved)

Case 3, patient OS, 38-year-old male, unemployed (main complaint) unmotivated, unable to concentrate, shy (patient history) family of four of parents and sister. Unmarried. After graduating from university, he worked with SE. Currently, he is living as a private investor withdrawn at home. When entering kindergarten, there was a separation anxiety disorder. The selective silence was around 5 years old, and the athletic meet in the elementary school was resting because I didn't want to be exposed to the public. I have been taking antidiabetic drugs for 5 months. Since June 2011, she has been depressed by psychosomatic medicine because she is depressed, self-disgusted, frustrated, and angry. I was still irritated and annoyed, with mood swings, overeating, and I wasn't feeling well, so I changed my doctor. There were frequent anxiety-depressing attacks once an hour. Recently there are several times a day. The contents include the situation of jealousy with the father, the face of the father's subordinates, the face of the disliked classmate, the face of the teacher in charge of elementary school.
(Diagnosis) Laboratory findings: Social anxiety disorder scale: 87, Leibovitz social anxiety disorder scale; 88, University of Tokyo egogram; W type (negative thinking). Diagnosis of social anxiety disorder, unspecified depression disorder, avoidable personality disorder.
(Prescription and progress) The contents of medication taken at the time of the visit are 2 dogmatils (50 mg), 2 depromail (25 mg), 2 bezadate (200 mg), 2 minutes, after breakfast and dinner. At the first visit, the following prescriptions were added to those already taken, Luran (4 mg) 3 tablets, Wipacs (0.5 mg) 3 tablets, Tasmoline (1 mg) 3 tablets, 3 minutes, 3 times after meal. Two weeks later, the flashback at home disappeared, but it still appears while driving. The content is a scene where I am complaining to my parents. Since the car only takes about 30 minutes a day, ADF has drastically decreased. The prescription continues as it is. After 4 weeks, the flashback disappeared completely. But very sleepy. I'm no longer frustrated, but I'm still not motivated.
(Changes in psychological examination findings 4 weeks after the first visit) Beck Depression Inventory 16 → 6, Self-Describing Depression Scale 53 → 45, Anxiety Depression Scale 51 → 0, Clinical Impression Scale Severity 5 (significant (Pathological symptoms) → 3 (mild pathological symptoms), clinical general impression scale improvement degree 1 (prominently improved).

Claims

A medicament for the treatment of depression having an invasive cognitive emotion, which has an anti-noradrenaline action, an anti-dopamine action, an anti-serotonin receptor 2 action and a serotonin 1A receptor partial agonist action.
The medicament according to claim 1, wherein the depression having an invasive cognitive emotion is atypical depression or post-traumatic stress disorder.
The medicament according to claim 1, wherein the depression having invasive cognitive emotion is atypical depression.
The medicament according to any one of claims 1 to 3, wherein the depression having an invasive cognitive emotion is a depression having an invasive cognitive emotion associated with panic disorder or social anxiety disorder.
The medicament according to any one of claims 1 to 4, which improves depression by suppressing anxiety / depressive attacks.
The medicine for treating depression having an invasive cognitive emotion contains at least any one compound selected from the group consisting of perospirone and lurasidone as an active ingredient in any one of claims 1 to 5. The pharmaceutical described.
The medicament according to any one of claims 1 to 6, wherein the medicament for treating depression having invasive cognitive emotion contains perospirone as an active ingredient.
The medicine according to claim 6 or 7, wherein the active ingredient is taken in a daily dose of 4 mg to 48 mg.
The combination medicine according to any one of claims 1 to 8, further comprising an additional drug for reducing akathisia, which is a side effect of the medicine.
The combination medicine according to claim 9, wherein the additional drug is an anticholinergic or benzodiazepine psychiatric drug.
The combined medicine according to any one of claims 1 to 10, further comprising components of an excipient, a binder and a lubricant.
The medicament according to claim 11, wherein the dosage form is a tablet.
Depression with invasive cognitive emotion of a composition comprising a compound or a pharmaceutically acceptable salt thereof, which has an anti-noradrenaline action, an anti-dopamine action, an anti-serotonin receptor 2 action and a serotonin 1A receptor partial agonist action Use as a therapeutic drug.