Comparison of depression with anxious distress and melancholic depression from the perspective of psychomotor disturbance

Abstract

Aim

In the DSM‐5, it is specified that severe cases of major depressive disorder with anxious distress (ANXD) may be accompanied with motor agitation. Agitation, on the other hand, is one of the main characteristics of major depressive disorder with melancholic features (MEL). The purpose of this study was to compare ANXD and MEL in terms of psychomotor disturbance.

Methods

A total of 106 patients with major depressive disorder were included in the study. Psychomotor disturbance was assessed using the CORE measure. The associations of ANXD and MEL with the CORE measure subscales of psychomotor retardation, agitation, and noninteractiveness were analyzed using multivariate logistic analysis.

Results

Retardation scores (odds ratio [OR] = 0.63, 95% confidence interval [CI] = 0.52–0.77) were associated with fewer diagnoses of ANXD, whereas agitation scores (OR = 2.23, 95% CI = 1.60–3.13) were associated with more diagnoses of ANXD. Both noninteractiveness (OR = 1.23, 95% CI = 1.06–1.42) and agitation (OR = 1.27, 95% CI = 1.02–1.58) scores were associated with increased diagnoses of MEL.

Conclusion

Among the characteristics of psychomotor disturbance, agitation is a common feature of both ANXD and MEL, and ANXD and the agitated type of MEL may be overlapping concepts. On the other hand, ANXD is distinguished from the retarded type of MEL by its low level of retardation, whereas MEL but not ANXD is characterized by noninteractiveness.

Agitation is a common feature of both depression with anxious distress (ANXD) and melancholic depression (MEL), suggesting that ANXD and the agitated type of MEL may be overlapping concepts. On the other hand, ANXD is distinguished from the retarded type of MEL by its low level of retardation, whereas MEL but not ANXD is characterized by noninteractiveness.

INTRODUCTION

Anxiety is a common symptom in patients with depression. ¹ , ² Patients with depression who show high levels of anxiety are clinically characterized as having a higher severity of depression, ³ , ⁴ , ⁵ higher risk of suicide, ³ , ⁶ , ⁷ , ⁸ lower response to antidepressants, ⁹ , ¹⁰ , ¹¹ slower recovery, ⁷ and higher chronicity ¹¹ than those who show low levels of anxiety. Thus, it is important to focus on the level of anxiety in the assessment of depression, and the importance of identifying patients with “anxious depression” has been emphasized. ³ , ⁷ The use of several different definitions of anxious depression in various studies has been problematic, ¹² , ¹³ but since the introduction of “anxious distress” as a specifier for major depressive disorder (MDD) in the DSM‐5, ¹⁴ this has become the primary definition.

MDD patients with anxious distress (ANXD), who are estimated to comprise 54%–78% of patients with MDD, ¹ have been identified as having the following clinical characteristics: higher severity of depression, ¹⁵ more frequent hospitalizations, ¹⁵ higher rate of suicidal ideation, ¹⁵ lower coping ability, ¹⁶ higher frequency of antidepressant side effects, ¹⁷ lower response to antidepressants, ¹⁷ and higher chronicity of illness ¹⁸ than MDD patients without anxious distress.

The diagnostic criteria for ANXD ¹⁴ defines severe cases as those that may be accompanied with motor agitation. On the other hand, depression with agitation has been conceptualized by Koukopoulos et al. ¹⁹ as mixed depression, emphasizing the usefulness of viewing it as a bipolar mixed state rather than a subtype of unipolar depression. ²⁰ Because the clinical features of mixed depression are similar to those of ANXD, the conceptual overlap between ANXD and mixed depression has recently been discussed. ²¹ , ²²

Psychomotor agitation is also a key feature of MDD with melancholic features (MEL). ²³ The criteria for MEL in DSM‐5 include items specifying psychomotor agitation. In addition, the clinical features of ANXD, such as the high severity of depression and high risk of suicide, appear to be shared with those of MEL. ²⁴ However, whether there any conceptual overlaps between ANXD and MEL remains unclear.

Several studies have suggested an association between anxious depression and MEL. In the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, Fava et al. ³ defined MDD with a baseline Hamilton Rating Scale for Depression Anxiety/Somatization factor score of 7 or higher as anxious depression, and suggested that anxious depression may share characteristics of MEL, such as loss of pleasure, psychomotor retardation/agitation, and decreased appetite/weight loss. In a different analysis of the STAR*D study, McGrath et al. ²⁴ also reported an association between MEL and anxious depression. On the other hand, the opposite has also been found, that is, Tundo et al. ²⁵ reported a lower frequency of MEL in patients with ANXD. Traditionally, anxiety has also been considered as a symptom associated with nonmelancholic depression. ²⁶ , ²⁷

On closer examination of the literature, melancholia has been shown to be a term used to describe a condition characterized by intense anxiety and psychomotor agitation. ¹⁹ Kraepelin established the concept of manic‐depressive illness in the sixth edition of his textbook ²⁸ but classified melancholia and manic‐depressive illness separately. The reason for this was that melancholia develops during the involutional age, is marked by anxiety, agitation, and delusions, and has an unfavorable prognosis, whereas manic‐depressive illness develops at a young age, is marked by psychomotor retardation, and was considered to have a favorable prognosis. However, Kraepelin ²⁹ subsequently incorporated melancholia into the concept of manic‐depressive illness, ³⁰ resulting in the agitated type of depression and the retarded type of depression being placed in the same category. In the DSM‐5, the diagnostic criteria for MEL include both psychomotor agitation and retardation.

The concept of mixed depression proposed by Koukopoulos, ¹⁹ which is based on the traditional definition of melancholia, is an attempt to identify patients with the agitated type of depression for therapeutic purposes. The association between ANXD and mixed depression suggests that the anxiety symptoms of ANXD are similar to those of melancholic agitation.

To our knowledge, no study to date has investigated the conceptual association between ANXD and MEL. In this study, we hypothesized that part of ANXD can be regarded as the agitated type of MEL and aimed to analyze the association between ANXD and MEL, focusing on psychomotor disturbance in patients with MDD.

METHODS

Subjects

A total of 106 patients with MDD were included in the study. Both inpatients and outpatients were included. These patients were from a case group included in our previous study. ³¹ All MDD patients were diagnosed, evaluated, and assigned to treatment by a psychiatrist with at least 5 years of experience. Inclusion criteria were as follows: (a) meeting the criteria for MDD in DSM‐5, (b) being 20–69 years old, and (c) having adequate ability to consent. Exclusion criteria were (a) having a serious physical illness, (b) having an organic psychiatric disorder, and (c) having severe suicidal ideations. The demographic information of the analyzed subjects is presented in Table 1. Patients were considered treatment‐resistant if they did not respond to two or more antidepressants of different pharmacological classes for 4 weeks. MEL and ANXD were diagnosed according to the DSM‐5. The evaluator assessed the subject's psychomotor disturbance when it was most severe using the CORE scale developed by Parker et al. ³² All subjects completed the Patient Health Questionnaire‐9 (PHQ‐9) ³³ at the time of study entry. All participants provided written consent to participate in the study. The study was conducted in accordance with the Declaration of Helsinki, and was approved by the Institutional Review Board of Toranomon Hospital (study approval no. 1516‐H).

Table 1.

Demographic and clinical characteristics and CORE scores of the 106 patients with MDD.

	ANXD (n = 39)	Non‐ANXD (n = 67)	P‐value	MEL (n = 52)	Non‐MEL (n = 54)	P‐value
Demographics
Age, years: mean (SD)	54.2 (11.9)	48.0 (13.7)	0.02*	51.2 (13.6)	49.4 (13.1)	0.50
Sex (male): n (%)	21 (53.8)	31 (46.3)	0.45	26 (50.0)	26 (48.1)	0.85
Education, years: mean (SD)	14.1 (2.2)	14.0 (2.0)	0.93	14.2 (2.0)	13.9 (2.2)	0.38
Marital status (married): n (%)	30 (76.9)	42 (62.7)	0.13	38 (73.1)	34 (63.0)	0.27
Number of offspring: mean (SD)	1.6 (1.0)	1.2 (1.1)	0.09	1.4 (0.9)	1.3 (1.2)	0.54
Employment status (employed): n (%)	24 (61.5)	37 (55.2)	0.53	26 (50.0)	35 (64.8)	0.12
Living alone: n (%)	5 (12.8)	11 (16.4)	0.62	5 (9.6)	11 (20.4)	0.12
Comorbid physical disease: n (%)	17 (43.6)	24 (35.8)	0.43	19 (36.5)	22 (40.7)	0.66
Comorbid psychiatric disorder: n (%)	5 (12.8)	3 (4.5)	0.14	1 (1.9)	7 (13.0)	0.06
Treatment setting (inpatients): n (%)	4 (10.3)	11 (16.4)	0.38	9 (17.3)	6 (11.1)	0.36
First‐degree relatives with a mood disorder: n (%)	11 (28.2)	15 (22.4)	0.50	8 (15.4)	18 (33.3)	0.03*
Clinical feature
Course of illness
Age of first episode: years (SD)	49.2 (14.2)	42.0 (13.3)	0.01*	46.7 (13.4)	42.6 (14.4)	0.12
Duration of MDD: years (SD)	5.1 (5.7)	6.0 (8.8)	0.54	4.5 (5.8)	6.9 (9.2)	0.21
Number of depressive episodes (SD)	2.1 (1.2)	2.2 (1.7)	0.62	2.0 (1.5)	2.3 (1.6)	0.29
Previous suicide attempts: n (%)	3 (7.7)	6 (9.0)	1.00	6 (11.5)	3 (5.6)	0.32
Treatment resistance: n (%)	9 (23.1)	10 (14.9)	0.29	8 (15.4)	11 (20.4)	0.50
Specifier in DSM‐5
Anxious distress: n (%)	−	−	−	16 (30.8)	23 (42.6)	0.21
Mixed features: n (%)	1 (2.6)	1 (1.5)	1.00	0 (0.0)	2 (3.7)	0.50
Melancholic features: n (%)	16 (41.0)	36 (53.7)	0.21	−	−	−
Atypical features: n (%)	2 (5.1)	1 (1.5)	0.55	1 (1.9)	2 (3.7)	1.00
Psychotic features: n (%)	3 (7.7)	4 (6.0)	0.71	6 (11.5)	1 (1.9)	0.04*
Peripartum onset: n (%)	0 (0.0)	1 (1.5)	1.00	1 (1.9)	0 (0.0)	0.49
Seasonal pattern: n (%)	1 (2.6)	0 (0.0)	0.37	1 (1.9)	0 (0.0)	0.49
PHQ‐9 score: mean (SD)	9.4 (6.3)	12.1 (7.5)	0.06	10.1 (7.8)	11.8 (6.3)	0.26
CORE score
Noninteractiveness: mean (SD)	5.1 (3.9)	6.0 (3.9)	0.27	7.4 (4.1)	4.0 (2.9)	<0.001**
Retardation: mean (SD)	3.7 (3.3)	6.8 (4.5)	<0.001**	7.3 (4.6)	4.1 (3.4)	<0.001**
Agitation: mean (SD)	4.5 (2.7)	2.6 (2.1)	<0.001**	4.3 (2.8)	2.3 (1.8)	<0.001**
Total: mean (SD)	13.4 (8.5)	15.3 (9.7)	0.29	19.0 (9.4)	10.4 (6.9)	<0.001**
Score ≥8: n (%)	27 (69.2)	50 (74.6)	0.55	46 (88.5)	31 (57.4)	<0.001**

Note: Continuous data were analyzed by the unpaired t‐test, and the comparison of categorical data were analyzed by the χ ² test and, when appropriate, with the Fisher's exact test.

Abbreviations: ANXD, major depressive disorder with anxious distress; DSM‐5, Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition; MEL, major depressive disorder with melancholic features; MDD, major depressive disorder; Non‐ANXD, major depressive disorder without anxious distress; Non‐MEL, major depressive disorder without melancholic features; PHQ‐9, Patient Health Questionnaire‐9; SD, standard deviation.

^* P < 0.05

^** P < 0.01.

Assessment measures

CORE measure

The CORE measure is a clinician‐rated scale developed by Parker et al. ³² that measures psychomotor disturbance in depressive disorders. The CORE measure consists of three subscales, namely, noninteractiveness, retardation, and agitation, which are evaluated using a total of 18 items. “Noninteractiveness” is a cognitive feature that leads to “pseudodementia” in depression, and represents the psychological aspect of psychomotor disturbance. Each item is scored from 0 to 3. The Noninteractiveness subscale consists of six items, with scores ranging from 0 to 18; the retardation subscale consists of seven items, with scores ranging from 0 to 21, and the agitation subscale consists of five items, with scores ranging from 0 to 15.

Scores are based on objective behavioral observations by the evaluator, and not on the patient's statements. Parker et al. proposed a cutoff value for the diagnosis of melancholia of a total CORE score of 8 or more, and stated that the total CORE score could be used as a continuous variable. In this study, CORE scores were used in the analysis as a continuous variable.

PHQ‐9

The PHQ‐9 is a rating scale for depressive symptoms that was developed for screening purposes by Spitzer et al. ³³ It is a self‐administered questionnaire and reflects the severity of depressive disorders. ³⁴ The total score of the Japanese version of the PHQ‐9 ³⁵ was used in this study as an indicator of the severity of depressive symptoms.

Data analysis

First, demographic and clinical characteristics were compared between the ANXD group and the MDD without anxious distress (non‐ANXD) group. Then, similar comparisons were made between the MEL group and the MDD without melancholic features (non‐MEL) group. For categorical data, the χ ² test and, where appropriate, the Fisher's exact test were used; for continuous data, the unpaired t‐test was used. Second, correlations among the three subscales of the CORE measure were analyzed. Third, multivariate logistic regression analysis was performed with the diagnostic category of ANXD or non‐ANXD as the dependent variable, and age and the scores on the three subscales of the CORE measure as independent variables. Multivariate logistic regression analysis was also performed with the diagnostic category of MEL or non‐MEL as the dependent variable, and age and the scores of the three subscales of the CORE as independent variables. The forward stepwise method was used in both analyses. Analyses were performed using SPSS Statistics version 28 software (IBM). A P‐value of less than 0.05 was considered to indicate a statistically significant difference between groups.

RESULTS

Demographic and clinical characteristics, and CORE subscale scores of the patients (Table 1)

Of the 106 MDD patients, 39 (36.8%) had ANXD, and of the 39 ANXD patients, 16 (41.0%) had an overlapping diagnosis of MEL. There was no difference in the prevalence of MEL between ANXD patients and non‐ANXD patients.

In a two‐group comparison of ANXD patients and non‐ANXD patients, ANXD patients were significantly older and had a significantly higher age of onset, CORE scores were significantly lower for retardation in ANXD patients and significantly higher for agitation in ANXD patients, and there were no significant differences in the severity of depression.

In a two‐group comparison of MEL patients and non‐MEL patients, family history of mood disorders in first‐degree relatives was significantly more frequent in non‐MEL patients than in MEL patients, psychotic features were significantly more frequent in MEL patients, and CORE scores for noninteractiveness, retardation, agitation scores, and total scores were all higher in MEL patients. There were no significant differences in the severity of depression between the two groups.

Correlation between CORE subscales

The correlations among the CORE subscale scores are shown in Table 2. There was a strong and positive correlation between noninteractiveness and retardation, and a moderate and positive correlation between noninteractiveness and agitation. The correlation between retardation and agitation was weak and positive.

Table 2.

Correlation (r) between CORE subscale scores in patients with MDD.

	Noninteractiveness	Retardation	Agitation
Noninteractiveness	−	0.774**	0.577**
Retardation	−	−	0.357**
Agitation	−	−	−

Abbreviations: MDD, major depressive disorder; r, Pearson's correlation coefficient.

^** P < 0.01.

Multivariate logistic regression analysis

The results of the multivariate logistic regression analysis of ANXD versus non‐ANXD as the dependent variable, and the scores of the three CORE subscales and age as independent variables are shown in Table 3. Retardation scores were associated with fewer diagnoses of ANXD, whereas agitation scores were associated with more diagnoses of ANXD. The discriminant accuracy rate was 77.4%.

Table 3.

Results of stepwise logistic regression analysis with ANXD/non‐ANXD as the dependent variable and CORE subscale scores as independent variables.

Variable
	B	SE	P‐value	OR	95% CI
Retardation	−0.46	0.10	<0.001	0.63	0.52–0.77
Agitation	0.80	0.17	<0.001	2.23	1.60–3.13
Constant	−0.94	0.48	0.05	0.39

Note: Fit index of this model: χ ² = 53.62 (P‐value < 0.001), Cox–Snell R ² = 0.40, Hosmer–Lemeshow test P = 0.07, predictive accuracy = 77.4%. Dependent variable: the diagnosis of ANXD (1) and non‐ANXD (0). Independent variables: age and scores of the three CORE subscales.

Abbreviations: ANXD, major depressive disorder with anxious distress; B, partial regression coefficient; CI, confidence interval; Non‐ANXD, major depressive disorder without anxious distress; OR, odds ratio; SE, standard error.

Next, Table 4 shows the results of multivariable logistic regression analysis with MEL versus non‐MEL as the dependent variable, and the scores of the three CORE subscales and age as independent variables. Noninteractiveness and psychomotor agitation were identified as statistically significant features distinguishing MEL from non‐MEL; both noninteractiveness and agitation scores were associated with increased diagnoses of MEL. The discriminant accuracy rate was 70.8%.

Table 4.

Results of stepwise logistic regression analysis with MEL/non‐MEL as the dependent variable and CORE subscale scores as independent variables.

Variable
	B	SE	P‐value	OR	95% CI
Noninteractiveness	0.20	0.08	0.007	1.23	1.06–1.42
Agitation	0.24	0.11	0.04	1.27	1.02–1.58
Constant	−1.89	0.46	<0.001	0.15

Note: Fit index of this model: χ ² = 26.66 (P‐value < 0.001), Cox–Snell R ² = 0.22, Hosmer–Lemeshow test P = 0.444, predictive accuracy = 70.8%. Dependent variable: the diagnosis of MEL (1) and non‐MEL (0). Independent variables: age and scores of the three CORE subscales.

Abbreviations: B, partial regression coefficient; CI, confidence interval; MEL, major depressive disorder with melancholic features; Non‐MEL, major depressive disorder without melancholic features; OR, odds ratio; SE, standard error.

Multicollinearity among the four items of age and scores of the three CORE subscales was investigated, but the variance inflation factor ranged from 1.2 to 3.4, and no multicollinearity was found.

DISCUSSION

The results of this study demonstrated that retardation was less frequent and agitation was more frequent in ANXD patients, as we hypothesized. Noninteractiveness and agitation were more frequent in MEL patients, and agitation was common in both ANXD and MEL patients. To our knowledge, this is the first study to compare the characteristics of ANXD and MEL from the perspective of psychomotor disturbance.

The definition of agitation in the CORE measure is agitation observed behaviorally, and includes apprehension and agitation that appears on the face, motor agitation such as rubbing, pacing, writhing, and wandering actions, and verbal stereotypy and stereotyped movements. ³² The diagnostic criteria for MEL includes an item for marked psychomotor agitation that is observable by others, ¹⁴ which overlaps with the definition in the CORE measure. On the other hand, the diagnostic criteria for ANXD are comprised mainly of subjective symptoms. The five criteria for ANXD are (1) feeling keyed up or tense, (2) feeling unusually restless, (3) difficulty concentrating because of worry, (4) fear that something awful may happen, and (5) feeling that the individual might lose control of himself or herself. Severe cases of ANXD may be accompanied by motor agitation. ¹⁴

The fact that patients with ANXD and patients with MEL commonly demonstrate behavioral agitation suggests that subjective anxiety symptoms are associated with objectively observable agitation. Indeed, anxiety and agitation are difficult to distinguish symptomatically. Tundo et al. ²¹ showed by network analysis that the item of “feeling keyed up or tense” in ANXD and the item of “psychic agitation or inner tension” in Koukopoulos’ mixed depression criteria ¹⁹ are almost indistinguishable. Parker et al. ³² suggest that it is advisable to interview the patient for at least 20 min and score the CORE to distinguish between anxiety and melancholic agitation. This is because anxiety symptoms may decrease as the relationship between the patient and the interviewer develops, but melancholic agitation often does not change no matter how much the interviewer tries to reassure the patient. Thus, ANXD and agitated MEL may overlap regarding the aspect of agitation.

Koukopoulos ¹⁹ argued that there are two types of anxiety in MDD patients. The first type of anxiety is an emotional reaction to the painful experience of depression itself, and this anxiety is improved by antidepressants. The second type of anxiety is anxiety as a form of excitement inherent in agitation itself. This type is considered to be the same as the agitation that occurs in MEL and mixed depression, which is often exacerbated by antidepressants and may improve with antipsychotics or electroconvulsive therapy. Our results suggest that the anxiety symptoms of ANXD may include the second type of anxiety discussed by Koukopoulos, supporting our hypothesis that a part of ANXD overlaps with the agitated type of MEL. This finding is also important in considering treatment strategies for ANXD, as it has been suggested that ANXD responds poorly to antidepressants. ¹⁷

On the other hand, patients with ANXD showed less psychomotor retardation, and hence the retarded type of MEL is distinct from ANXD. The fact that some prior studies have shown that anxious depression is associated with MEL in some studies, ³ , ²⁴ whereas another study did not find an association ²⁵ may be owing to the fact that the retarded and agitated types of MEL were not distinguished. In the DSM‐5, ¹⁴ agitation and retardation are included as a single item in the MDD and MEL criteria, but they should be separate items.

In this study, noninteractiveness was a characteristic of MEL in addition to agitation; patients with noninteractiveness are inattentive, with moods that do not respond to the interviewer's prompts, make brief responses, and talk about topics and themes that are not rich. Patients who demonstrate noninteractiveness do not respond to social cues during the interview, which may lead the interviewer to feel that the patient is not registering the interviewer. ³² According to Parker et al., ³² , ³⁶ this is the cognitive aspect of psychomotor disturbance, which can lead to pseudodementia or stupor.

In the present study, patients with ANXD were significantly older than those with non‐ANXD. In the STAR*D study, ³ patients with anxious depression were significantly older than those with nonanxious depression, which was consistent with our results. However, Otsubo et al. ³⁷ reported that patients with ANXD were significantly younger than those with non‐ANXD. This indicates that the inconsistency of the age of ANXD patients may be owing to the populations used in the studies.

The lack of a difference in the duration of illness and rate of suicide attempts between ANXD and non‐ANXD patients in our sample is inconsistent with the DSM‐5 commentary. ¹⁴ The proportion of patients with ANXD (36.8%) was also lower than that in previous studies (54%–78%). ¹ These inconsistencies may be partly due to the fact that the study population was mainly outpatients, and many of the patients in our study hence had relatively mild symptoms.

The present study has several limitations that should be considered. First, the small sample size and the fact that we did not use structured interviews in our diagnosis may limit the generalizability of our results. Second, we only investigated the presence of ANXD, and did not assess the severity of ANXD; further analysis including the assessment of ANXD severity is needed to investigate the association between ANXD and MEL. Third, the present study is based on data comparing depression with and without anxious distress and depression with and without melancholic features, respectively. ANXD and MEL were not directly compared, and in interpreting the results, it is necessary to take into account the presence of subjects with combined ANXD and MEL. Fourth, most of the subjects in this study were outpatients, and most of them had depression of mild to moderate in severity. Because agitated depression is often severe and a problem in clinical practice, there may be certain limitations in the generalizability of the results of this study. Finally, our study included patients who did not meet the recommendation of Parker et al. of undergoing at least 20 min of interview time in the assessment of the CORE measure. ³² This may have affected the distinction between anxiety and melancholic agitation in our study.

Future research should focus on patients with ANXD, including those with severe cases, and compare the effectiveness of not only antidepressants but also antipsychotics and electroconvulsive therapy. If it is found that antidepressants are not recommended for ANXD, despite it being a subtype of MDD, this would constitute a significant clinical insight.

In conclusion, we showed that agitation is a common feature of both ANXD and MEL among patients with psychomotor disturbance, suggesting that ANXD and the agitated type of MEL may be overlapping concepts. On the other hand, ANXD is distinguished from the retarded type of MEL by its low level of retardation, whereas MEL but not ANXD is characterized by noninteractiveness.

AUTHOR CONTRIBUTIONS

Y.T.: Conceptualization, methodology, formal analysis, investigation, data curation, writing—original draft, project administration, funding acquisition. T.I.: Conceptualization, methodology, formal analysis, data curation, writing—review and editing, supervision. A.S.: Investigation, data curation, writing—review and editing. H.T.: Investigation, data curation, writing—review and editing. M.T.: Investigation, data curation, writing—review and editing. M.S.: Investigation, data curation, writing—review and editing. Y.F.: Writing—review and editing, supervision. S.O.: Conceptualization, writing–review and editing, supervision. All authors contributed to and have approved the final manuscript.

CONFLICT OF INTEREST STATEMENT

Hiroyuki Toda is a Field Editor of Psychiatry and Clinical Neurosciences Reports and a co‐author of this article. He was excluded from editorial decision‐making related to the acceptance and publication of this article. Yu Tamada has received honoraria from Otsuka Pharmaceutical, Sumitomo Pharma, Eisai, MSD, and Meiji Seika Pharma. Takeshi Inoue has received personal compensation from Mochida Pharmaceutical, Takeda Pharmaceutical, Eli Lilly, Janssen Pharmaceutical, MSD, Taisho Toyama Pharmaceutical, Yoshitomiyakuhin, and Daiichi Sankyo; grants from Shionogi, Astellas, Tsumura, and Eisai; and grants and personal compensation from Otsuka Pharmaceutical, Sumitomo Pharma, Mitsubishi Tanabe Pharma, Kyowa Pharmaceutical Industry, Pfizer, Novartis Pharma, and Meiji Seika Pharma; and is a member of the advisory boards of Pfizer, Novartis Pharma, and Mitsubishi Tanabe Pharma. Atsushi Sekine has received personal compensation from Otsuka Pharmaceutical, Meiji Seika Pharma, Takeda Pharmaceutical, and Sumitomo Pharma. Hiroyuki Toda has received lecture fees from Sumitomo Pharma, Otsuka Pharmaceutical, Takeda Pharmaceutical, Pfizer, Yoshitomi Pharmaceutical, and Viatris. Minoru Takeshima has received lecture fees from Kyowa Pharmaceutical, Otsuka Pharmaceutical, Sumitomo Pharma, Takeda Pharmaceutical, and Lundbeck. Masaaki Sasaki has received lecture fees from Viatris. Yota Fujimura has received honoraria from Sumitomo Pharma, and research grants from Shionogi and Sumitomo Pharma. Susumu Ohmae has received honoraria from Viatris and Takeda Pharmaceutical.

ETHICS APPROVAL STATEMENT

This study protocol was reviewed and approved by the Institutional Review Board of Toranomon Hospital, approval number [1516‐H].

PATIENT CONSENT STATEMENT

All participants provided written consent to participate in the study.

CLINICAL TRIAL REGISTRATION

N/A.

Tamada Y, Inoue T, Sekine A, Toda H, Takeshima M, Sasaki M, et al. Comparison of depression with anxious distress and melancholic depression from the perspective of psychomotor disturbance. Psychiatry Clin Neurosci Rep. 2024;3:e70022. 10.1002/pcn5.70022

DATA AVAILABILITY STATEMENT

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.