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(TITLE ( depression OR “ Depressive Disorder ”) AND TITLE (“ Social Determinants of Health ” OR tryptophan OR glucocorticoids OR neurology OR genes OR neurogenesis OR “ Neuronal Plasticity ” OR kynurenine OR genetics OR “ Neurogenic Inflammation ” OR “ Gastrointestinal Microbiome ” OR “ Genome-Wide Association Study ” OR “ Gene-Environment Interaction ” OR aetiology OR etiology )) OR TITLE ( cause* W/3 ( depression OR depressive )).
O.R. was responsible for the design of the study and methodology undertaken. Despite P.T.’s involvement in YPMH, he had no role in the design of the study; P.T. was responsible for the conceptualization of the study. Validation was conducted by O.R. and J.F.M. Formal analysis (data charting) was undertaken by O.R. O.R. and P.T. were involved in the investigation, resource acquisition, and data presentation. The original draft preparation was undertaken by O.R. The writing was conducted by O.R., with review and editing by P.T. and J.F.M. Funding acquisition was undertaken by O.R. and P.T. All authors have read and agreed to the published version of the manuscript.
This research was funded by The William Templeton Foundation for Young People’s Mental Health, Cambridge Philosophical Society, and the Aviva Foundation.
The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.
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Depression needs a personalized, holistic approach for effective management..
Posted August 14, 2024 | Reviewed by Davia Sills
"Whatever you lack, you must borrow from yourself." — Cato
The term “ depression ” has evolved significantly over time, reflecting the changing ways in which society understands and describes this complex condition. From the ancient concept of “black bile” in Hippocratic medicine to the existential “pain of existence” and the romantic “spleen,” depression has long been a topic of interest not only to doctors and psychologists but also to intellectuals and religious figures.
In modern times, depression is often labeled as the “disorder of the century,” a term that captures the widespread and varied nature of this “obscure illness.” This article delves into the many faces of depression, emphasizing that it is not just a single mood but a multifaceted condition requiring a comprehensive approach to treatment.
Depression is not a one-size-fits-all condition. Its manifestations can range from mild to severe, and it can be a temporary phase or a long-term condition integrated into a person’s way of life. Understanding depression requires recognizing that each person’s experience is different, and thus, their treatment needs will differ as well (Yapko, 2018).
The evolution of the term “depression” highlights its complexity. Historically, depression has been associated with various emotional states and conditions, and modern psychiatry now groups the causes of depression into three primary domains: biological, psychological, and social. Biological factors include neurochemistry, genetic predispositions, and the effects of certain diseases or medications (Yapko, 2018). Psychological factors encompass a person’s individual history, trauma exposure, and coping mechanisms. Social factors involve the relationships people maintain, the culture they grow up in, and the family dynamics they experience (Yapko, 2018).
This bio-psycho-social model illustrates that depression is not merely a chemical imbalance in the brain—a misconception perpetuated by the pharmaceutical industry since the advent of antidepressants like Prozac in the late 1980s (Lacasse & Leo, 2005). Although these medications can be beneficial for managing certain symptoms, they do not address the underlying causes of depression, such as poor coping skills, lack of a support network, or unresolved trauma (Yapko, 2018).
While antidepressants can help alleviate some symptoms of depression, they are not a cure-all. The social use of the term “depression” has led to its frequent abuse and, unfortunately, its misuse in describing a wide range of moods and conditions.
This over-simplification often leads to an overreliance on medications, which cannot teach essential life skills such as problem-solving, building healthy relationships, or managing stress . Overreliance on medication without addressing these broader issues often leads to undertreatment, which can exacerbate the condition in the long run (Deacon & Abramowitz, 2005).
Furthermore, the narrative that depression is solely due to a chemical imbalance has been largely discredited by recent research. The simplistic view that a pill can “fix” depression ignores the complexity of the condition and can lead to disappointment and relapse . Effective treatment must, therefore, be holistic, incorporating therapy to build life skills and foster a deeper understanding of oneself and one’s risk factors (Moncrieff et al., 2022).
Psychotherapy plays a crucial role in helping individuals with their perceptions and relationships that give rise to depression. A skilled therapist can help identify the unique vulnerabilities, behaviors, and contexts that exacerbate and maintain depression in each person. This personalized approach allows individuals to develop coping strategies that are tailored to their specific needs and circumstances (Yapko, 2018).
The goal of therapy is not to “cure” depression but to transform the person’s perception of themselves and their relationship with their reality. It also equips individuals with the tools they need to manage their moods and themselves on an ongoing basis. This includes learning to recognize depressive patterns, developing better problem-solving skills, and creating a better social and relational environment (Gibson, 2024; Beck, 1979).
For those in a relationship with someone who is depressed, it is important to find a balance between being supportive and avoiding enabling self-defeating behaviors to continue. It’s crucial to encourage the depressed individual to seek help and engage in activities that can lift their mood, even if they initially resist. However, it’s equally important for the partner to take care of their well-being and not allow depression to dominate their life (Yapko, 2018).
Supporting a loved one with depression also involves setting boundaries . It’s essential to communicate that while the feelings of the depressed person are valid, they do not justify harmful behaviors or the neglect of their own needs or those of the relationship (Coyne, 1976). This understanding is part of the broader context in which depression, as a term and a condition, is often misused or misunderstood.
One of the most effective ways to counteract depression is through positive action. While depression often leads to passivity and a feeling of helplessness, taking small steps toward engaging with life and disrupting the current defeatist perception can create a positive feedback loop that improves mood and builds momentum. This could be as simple as taking a walk, engaging in a hobby, or socializing with friends (Jacobson et al., 1996), basically not surrendering to the problem (Gibson, 2024).
However, these actions must be taken with the right support and preparation. A person with depression may need to develop certain skills before they can successfully engage in these activities without feeling overwhelmed. This is where therapy and the support of loved ones play a critical role (Gibson, 2024).
Depression, as a term and a condition, has evolved significantly over the centuries, reflecting its complex and multi-dimensional nature. While medication can help alleviate some symptoms, it is not a standalone solution. Therapy, support from loved ones, and a proactive approach to building life skills and coping mechanisms are essential for managing depression effectively (Beck, 1979; Gibson, 2024).
For those supporting a loved one with depression, it’s important to be both supportive and self-caring, encouraging positive action without allowing the depression to dictate the terms of the relationship. With the right approach, it is possible to manage depression and lead a fulfilling life despite the challenges it presents (Yapko, 2018).
Beck, A. T. (1979). Cognitive therapy and emotional disorders . Penguin.
Coyne, J. C. (1976). Depression and the response of others. Journal of Abnormal Psychology, 85 (2), 186–193.
Deacon, B. J., & Abramowitz, J. S. (2005). The short-term efficacy of psychological treatments for depression: A meta-analysis. Clinical Psychology Review, 25 (4), 401–419.
Gibson, P. (2024). When The Bubble Bursts. A New Approach to Treating Depression. Strategic Science Books.
Jacobson, N. S., Martell, C. R., & Dimidjian, S. (2001). Behavioural activation treatment for depression: Returning to contextual roots. Clinical Psychology: Science and Practice, 8 (3), 255–270.
Lacasse, J. R., & Leo, J. (2005). Serotonin and depression: A disconnect between the advertisements and the scientific literature. PLoS Medicine, 2 (12), e392.
Moncrieff, J., Cooper, R. E., Stockmann, T., Amendola, S., Hengartner, M. P., & Horowitz, M. A. (2022). The serotonin theory of depression: A systematic umbrella review of the evidence. Molecular Psychiatry, 27 (6), 2402–2414.
Yapko, M. D. (2018). Keys to unlocking depression: An integrated approach to healing . Yapko Publications.
Padraic Gibson, D.Psych, is a Consultant Clinical Psychotherapist and is the Clinical Director of The OCD Clinic®, and director of Training and Organization Consultation at The Coaching Clinic®, Dublin. He is senior research associate at Dublin City University.
Sticking up for yourself is no easy task. But there are concrete skills you can use to hone your assertiveness and advocate for yourself.
Everyone experiences sadness at times. But depression is something more. Depression is extreme sadness or despair that lasts more than days. It interferes with the activities of daily life and can cause physical symptoms such as pain, weight loss or gain, sleeping pattern disruptions, or lack of energy.
People with depression may also experience an inability to concentrate, feelings of worthlessness or excessive guilt, and recurrent thoughts of death or suicide.
Depression is the most common mental disorder. Fortunately, depression is treatable. A combination of therapy and antidepressant medication can help ensure recovery.
Adapted from the Encyclopedia of Psychology
Antidepressant use among teen girls and young women
No such rise among teen boys and young men during and after the COVID-19 pandemic
Improving concussion care
Psychologists’ important role in treating anxiety and depression after concussions
Effective treatment for autistic adults
There are few, if any, support services for autistic people transitioning to adulthood.
Chronic pain is linked to depression and anxiety
Many also experience work limitations, difficulty completing errands alone, and trouble taking part in social activities
More resources about depression
Clinical Practice Guideline for the Treatment of Depression
Not So Abnormal Psychology
Treatment of Late-Life Depression, Anxiety, Trauma, and Substance Abuse
Treatment of Psychosocial Risk Factors in Depression
Treating Depression, Anxiety, and Stress in Ethnic and Racial Groups
Interpersonal Reconstructive Therapy for Anger, Anxiety, and Depression
Pockets Full of Rocks
Danny and the Blue Cloud
Why Are You So Sad?
Exceptional Canadian Contributions to Research in Depression / Les contributions canadiennes exceptionnelles à la recherche sur la dépression
a After completing the prescreening questionnaire, people were deemed ineligible if they were currently using antidepressant medication (n = 157); lived outside reasonable commuting distance (n = 161); did not meet criteria for the magnetic resonance imaging scans (n = 99); had a first- or second-degree relative with a diagnosis of schizophrenia spectrum, bipolar I or II, or other psychotic disorder ( = 77); had a recent history of substance use disorder (n = 50); opted out of in-person screening (n = 38); were not in a current depressive episode (n = 37); were more than 25% beyond the upper or lower range of recommended body weight (n = 32); had a medically significant suicide attempt (n = 30); had lifetime hallucinogen use that exceeded the exclusion threshold (n = 30); if major depressive disorder (MDD) was not primary psychiatric diagnosis (n = 18); if they had a medical exclusion (n = 11); had exclusionary use of nonserotonergic psychoactive medication (n = 11); or failed to respond to electroconvulsive therapy during current depressive episode (n = 4). Forty-five people were ineligible for other reasons.
b People were deemed ineligible during in-person screening if they had a psychiatric condition judged to be incompatible with establishment of rapport or safe exposure to psilocybin (n = 17); did not have confirmed DSM-5 diagnosis of MDD (n = 7); had a recent history of moderate to severe substance use disorder (n = 5); were at high risk for suicidality (n = 3); disagreed with study procedures (n = 3); had a baseline GRID Hamilton Depression Rating Scale score lower than the eligibility threshold of 17 (n = 2); had cardiovascular conditions (n = 2); had lifetime hallucinogen use that exceeded the exclusion threshold (n = 2); were currently taking serotonergic medication (n = 1); or were more than 25% beyond the upper and lower range of recommended body weight (n = 1).
c Dropped out of the study due to anticipatory anxiety about the upcoming first psilocybin session.
d Dropped out of study due to sleep difficulties. Sleep difficulties were also reported at screening, and it was not clear whether sleep difficulties were exacerbated by the intervention.
e Participant showed a marked reduction in depression symptoms immediately following the first psilocybin session and chose not to proceed with the intervention.
GRID-HAMD indicates GRID Hamilton Depression Rating Scale.
Data points are presented as mean (SD). In the immediate treatment group (n = 13), weeks 5 and 8 correspond to weeks 1 and 4 after the psilocybin session 2. In the delayed treatment group (n = 11), weeks 5 and 8 are prepsilocybin assessments obtained during the delay period. Effect sizes (Cohen d with 95% CI) and P values reflect the results of a 2-sample t test between the 2 groups at week 5 (Cohen d = 2.5; 95% CI, 1.4-3.5; P < .001) and week 8 (Cohen d = 2.6; 95% CI, 1.5-3.7; P < .001).
The mean (SD) GRID-HAMD score was 22.8 (3.9) at baseline, 8.7 (7.6) at week 1, and 8.9 (7.4) at week 4. Effect sizes (Cohen d with 95% CI) and P values reflect the results of a paired sample t test that compared scores between baseline and week 1 (Cohen d = 2.3; 95% CI, 1.5-3.1; P < .001) and week 4 postsession-2 follow-up (Cohen d = 2.3; 95% CI, 1.5-3.1; P < .001).
Trial protocol
eTable 1. Repeated Measures ANOVAs Comparing Depression, Anxiety, and Suicidal Ideation Outcomes at Each Timepoint by Treatment Condition
eTable 2. t Tests Comparing Depression, Anxiety, and Suicidal Ideation Outcomes at Each Timepoint by Condition
eTable 3. Repeated Measures ANOVAs and Effect Sizes for Depression, Anxiety, and Suicidal Ideation Outcomes Across Overall Sample
eTable 4. Ratings of Personal Meaning, Spiritual Significance, Psychological Challenge, and Psychological Insight During Each of Two Psilocybin Sessions
eTable 5. Mean Proportion (and Standard Deviation) of Total Possible Score on the Mystical and Challenging Experiences Questionnaires During Each of Two Psilocybin Sessions; Proportion of Participants Who Had a Complete Mystical Experience in Each Session
eTable 6. Monitor Ratings of Peak Psilocybin Effects During Each of Two Psilocybin Sessions
eTable 7. Mean of the Peak Heart Rate and Blood Pressure Across Participants During Each of Two Psilocybin Sessions. Data Regarding Number of Participants Requiring Increased Rate of Monitoring
eTable 8. Adverse Emotional and Physical Effects During Psilocybin Sessions
eTable 9. Adverse Effects Reported the Day After Sessions 1 and 2 That Were Rated by Staff as Possibly or Probably Related to Psilocybin
eTable 10. Initiation of Antidepressant Medication, Psychotherapy, or Psilocybin Reported 4 weeks After Session 2
eFigure 1. Decrease in Depression Scores on the Quick Inventory of Depression Symptoms (QIDS-SR) from Baseline to 1-day Post Psilocybin Session 1 and Through the 4-week Follow-up
eFigure 2. Comparison of Depression Scores on the Quick Inventory of Depression Symptoms (QIDS-SR) by Treatment Condition
eFigure 3. Comparison of Depression Scores on the Beck Depression Inventory – II (BDI-II) by Treatment Condition
eFigure 4. Comparison of Depression Scores on the Patient Health Questionnaire – 9 Item (PHQ-9) by Treatment Condition
eFigure 5. Comparison of Anxiety Scores on the Hamilton Anxiety Scale (HAM-A) by Treatment Condition (Immediate vs Delayed). Effect Size Calculation Using Cohen’s d Statistic
eFigure 6. Comparison of Anxiety Scores on the State-Trait Anxiety Inventory – State Subscale (STAI-State) by Treatment Condition
eFigure 7. Comparison of Anxiety Scores on the State-Trait Anxiety Inventory – Trait Subscale (STAI-Trait) by Treatment Condition
eFigure 8. Comparison of Anxiety Scores on the State-Trait Anxiety Inventory – Total Scale (STAI-Total) by Treatment Condition
eFigure 9. Comparison of Suicidal Ideation Scores on the Columbia Suicide Severity Rating Scale (CSSRS) by Treatment Condition
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Davis AK , Barrett FS , May DG, et al. Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder : A Randomized Clinical Trial . JAMA Psychiatry. 2021;78(5):481–489. doi:10.1001/jamapsychiatry.2020.3285
© 2024
Question Is psilocybin-assisted therapy efficacious among patients with major depressive disorder?
Findings In this randomized clinical trial of 24 participants with major depressive disorder, participants who received immediate psilocybin-assisted therapy compared with delayed treatment showed improvement in blinded clinician rater–assessed depression severity and in self-reported secondary outcomes through the 1-month follow-up.
Meaning This randomized clinical trial found that psilocybin-assisted therapy was efficacious in producing large, rapid, and sustained antidepressant effects in patients with major depressive disorder.
Importance Major depressive disorder (MDD) is a substantial public health burden, but current treatments have limited effectiveness and adherence. Recent evidence suggests that 1 or 2 administrations of psilocybin with psychological support produces antidepressant effects in patients with cancer and in those with treatment-resistant depression.
Objective To investigate the effect of psilocybin therapy in patients with MDD.
Design, Setting, and Participants This randomized, waiting list–controlled clinical trial was conducted at the Center for Psychedelic and Consciousness Research at Johns Hopkins Bayview Medical Center in Baltimore, Maryland. Adults aged 21 to 75 years with an MDD diagnosis, not currently using antidepressant medications, and without histories of psychotic disorder, serious suicide attempt, or hospitalization were eligible to participate. Enrollment occurred between August 2017 and April 2019, and the 4-week primary outcome assessments were completed in July 2019. A total of 27 participants were randomized to an immediate treatment condition group (n = 15) or delayed treatment condition group (waiting list control condition; n = 12). Data analysis was conducted from July 1, 2019, to July 31, 2020, and included participants who completed the intervention (evaluable population).
Interventions Two psilocybin sessions (session 1: 20 mg/70 kg; session 2: 30 mg/70 kg) were given (administered in opaque gelatin capsules with approximately 100 mL of water) in the context of supportive psychotherapy (approximately 11 hours). Participants were randomized to begin treatment immediately or after an 8-week delay.
Main Outcomes and Measures The primary outcome, depression severity was assessed with the GRID-Hamilton Depression Rating Scale (GRID-HAMD) scores at baseline (score of ≥17 required for enrollment) and weeks 5 and 8 after enrollment for the delayed treatment group, which corresponded to weeks 1 and 4 after the intervention for the immediate treatment group. Secondary outcomes included the Quick Inventory of Depressive Symptomatology-Self Rated (QIDS-SR).
Results Of the randomized participants, 24 of 27 (89%) completed the intervention and the week 1 and week 4 postsession assessments. This population had a mean (SD) age of 39.8 (12.2) years, was composed of 16 women (67%), and had a mean (SD) baseline GRID-HAMD score of 22.8 (3.9). The mean (SD) GRID-HAMD scores at weeks 1 and 4 (8.0 [7.1] and 8.5 [5.7]) in the immediate treatment group were statistically significantly lower than the scores at the comparable time points of weeks 5 and 8 (23.8 [5.4] and 23.5 [6.0]) in the delayed treatment group. The effect sizes were large at week 5 (Cohen d = 2.5; 95% CI, 1.4-3.5; P < .001) and week 8 (Cohen d = 2.6; 95% CI, 1.5-3.7; P < .001). The QIDS-SR documented a rapid decrease in mean (SD) depression score from baseline to day 1 after session 1 (16.7 [3.5] vs 6.3 [4.4]; Cohen d = 2.6; 95% CI, 1.8-3.5; P < .001), which remained statistically significantly reduced through the week 4 follow-up (6.0 [5.7]; Cohen d = 2.3; 95% CI, 1.5-3.0; P < .001). In the overall sample, 17 participants (71%) at week 1 and 17 (71%) at week 4 had a clinically significant response to the intervention (≥50% reduction in GRID-HAMD score), and 14 participants (58%) at week 1 and 13 participants (54%) at week 4 were in remission (≤7 GRID-HAMD score).
Conclusions and Relevance Findings suggest that psilocybin with therapy is efficacious in treating MDD, thus extending the results of previous studies of this intervention in patients with cancer and depression and of a nonrandomized study in patients with treatment-resistant depression.
Trial Registration ClinicalTrials.gov Identifier: NCT03181529
Major depressive disorder (MDD) is a substantial public health concern, affecting more than 300 million individuals worldwide. Depression is the number one cause of disability, 1 and the relative risk of all-cause mortality for those with depression is 1.7 times greater than the risk for the general public. 2 In the United States, approximately 10% of the adult population has been diagnosed with MDD in the past 12 months, 3 and the yearly economic burden of MDD is estimated to be $210 billion. 4
Although effective pharmacotherapies for depression are available, these drugs have limited efficacy, produce adverse effects, and are associated with patient adherence problems. 5 Although many patients with depression showed reduced or remitted symptoms after treatment with existing pharmacotherapies, 6 approximately 30% to 50% of patients did not respond fully and as many as 10% to 30% of patients were considered treatment-resistant, resulting in average effects that were only modestly larger than the effects of placebo. 7 , 8
Most of the current pharmacotherapies for MDD, including the widely used selective serotonin reuptake inhibitors, increase levels of brain monoamine neurotransmitters such as serotonin and norepinephrine (typically by blocking reuptake). 6 A growing body of evidence suggests that newer ketamine-like medications exert therapeutic efficacy in MDD through effects on glutamate neurotransmission. 9 , 10 Ketamine hydrochloride, a nonselective N -methyl- d -aspartate receptor antagonist, is the most well-researched of these newer medications. Several studies have demonstrated the efficacy of a single ketamine infusion in rapidly (within hours) reducing depression symptoms and, when effective, lasting from a few days to about 2 weeks. 10 , 11 However, ketamine has high abuse liability, and its administration involves moderate physiological risk that requires medical monitoring. 12
Quiz Ref ID The combined serotonergic and glutamatergic action of psilocybin 13 - 15 (a classic hallucinogen) and the preliminary evidence of the antidepressant effects of psilocybin-assisted therapy (among patients with life-threatening cancer or patients with treatment-resistant depression) 16 - 18 indicate the potential of psilocybin-assisted therapy as a novel antidepressant intervention. 19 Moreover, psilocybin has lower addiction liability and toxic effects compared with ketamine 20 - 22 and is generally not associated with long-term perceptual, cognitive, or neurological dysfunction. 23
The substantial negative public health impact of MDD underscores the importance of conducting more research into drugs with rapid and sustained antidepressant effects. Current pharmacotherapies for depression have variable efficacy and unwanted adverse effects. Novel antidepressants with rapid and sustained effects on mood and cognition could represent a breakthrough in the treatment of depression and may potentially improve or save lives. Therefore, the primary objective of this randomized clinical trial was to investigate the effect of psilocybin therapy in patients with MDD.
This randomized, waiting list–controlled clinical trial was conducted at the Center for Psychedelic and Consciousness Research in Baltimore, Maryland. The Johns Hopkins Medicine Institutional Review Board approved this trial (the protocol is included in Supplement 1 ). Written informed consent was obtained from all participants.
This trial of psilocybin therapy included participants with moderate or severe MDD episodes, as assessed with the Structured Clinical Interview for DSM-5 (SCID-5) 24 and the GRID-Hamilton Depression Rating Scale (GRID-HAMD; a score of ≥17 was required for enrollment). 25 , 26 Eligible candidates were aged 21 to 75 years who self-reported no current pharmacotherapy for depression at trial screening. To avoid the confounding effects and potential interactions of concurrent antidepressant use, candidates were required to refrain from using antidepressants (eg, selective serotonin reuptake inhibitors) for at least 5 half-lives before the screening and up to 4 months after enrollment (through the completion of the primary outcome assessment). However, the decision to taper off and/or continuing not to take their medications during the study was made by the individuals and their prescribing physicians and not by study personnel. Additional eligibility requirements included being medically stable with no uncontrolled cardiovascular conditions; having no personal or family history (first or second degree) of psychotic or bipolar disorders; and, for women, being nonpregnant, being non-nursing, and agreeing to use contraception. Individuals with a moderate or severe alcohol or other drug use disorder (including nicotine) in the past year, as defined by Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) ( DSM-5 ) criteria, were excluded, as were individuals with substantial lifetime use (>10 total) or recent use (past 6 months) of ketamine or classic hallucinogens, such as psilocybin-containing mushrooms or lysergic acid diethylamide (eMethods in Supplement 2 ).
Participants were enrolled between August 2017 and April 2019, and the 4-week primary outcome assessments were completed in July 2019. Recruitment was carried out through flyers, print advertisements, internet forums, social media, and the study website. Of the 870 individuals screened by telephone or electronic screening survey, 70 went on to undergo in-person medical and psychological screening, 43 were disqualified, and 27 qualified and were enrolled in the study. After screening, baseline assessments, and enrollment, 27 participants were randomized to either the immediate treatment group or the delayed treatment group (ie, the waiting list control condition). The use of a delayed treatment control was chosen to differentiate the psilocybin intervention from spontaneous symptom improvement. The delay interval was 8 weeks, after which participants in the delayed treatment group underwent all study assessments and entered the study intervention period. Randomization to the immediate treatment and delayed treatment groups occurred after screening and baseline assessments ( Figure 1 ). Participants were randomized using urn randomization, 27 balancing for sex, age, depression severity at screening (assessed using the GRID-HAMD), and level of treatment resistance (assessed using the Maudsley Staging Method). 28 One of us (F.S.B.), who was not involved in participant screening or enrollment, performed urn randomization using the randPack library, version 1.32.0, 29 in the R Statistical Software package (R Foundation for Statistical Computing). 30
Participants received no monetary compensation for undergoing the intervention. However, participants received a total of $200 for completing 2 magnetic resonance imaging sessions.
Quiz Ref ID The intervention period was 8 weeks and involved at least 18 in-person visits, including 2 daylong psilocybin administration sessions ( Figure 2 ). Consistent with previous studies using psilocybin, 16 , 31 the visit schedule included preparatory meetings (8 hours in total) with 2 session facilitators before the first psilocybin session as well as follow-up meetings after psilocybin sessions (2-3 hours in total) (eMethods in Supplement 2 ). Session facilitators were study staff with varying educational levels (ie, bachelor’s, master’s, doctorate, and medical degrees) and professional disciplines (eg, social work, psychology, and psychiatry). After the preparation meetings, 2 psilocybin administration sessions were conducted a mean of 1.6 weeks apart (no statistically significant differences were found between conditions; eResults in Supplement 2 ). The psilocybin dose was moderately high (20 mg/70 kg) in session 1 and was high (30 mg/70 kg) in session 2. Procedures for psilocybin administration and the conduct of the sessions were similar to procedures used in previous and ongoing studies with psilocybin (eMethods in Supplement 2 ) at the Center for Psychedelic and Consciousness Research. 16 , 32 , 33
Psilocybin was administered in opaque gelatin capsules with approximately 100 mL water. Both facilitators were present in the room and available to respond to participants’ physical and emotional needs during the day-long session, with the exception of short breaks taken by 1 facilitator at a time. During the session, participants were instructed to lie on a couch in a living room–like environment, and facilitators encouraged participants to focus their attention inward and stay with any experience that arose. To enhance inward reflection, music was played (the playlist is provided in the eMethods in Supplement 2 ), and participants were instructed to wear eyeshades and headphones.
For safety during the 8-week delay period of the delayed treatment group, participants were monitored weekly by in-person assessment or brief telephone calls. In weeks 5 and 8, participants attended an in-person visit and underwent the GRID-HAMD assessment and other study measures. In other weeks of the delay period, participants received telephone calls that included a brief check-in and assessment for self-reported suicidal ideation or behavior and depression symptoms. All assessments during the delay period were administered by study staff who were not lead facilitators. At the end of the delay period, all participants in the delayed treatment group completed the same intervention as the participants in the immediate treatment group.
Screening evaluation included a preliminary questionnaire administered via telephone or an online survey as well as an in-person medical history and physical examination, electrocardiogram, routine medical blood and urinalysis laboratory tests, and structured assessments (eg, SCID-5, SCID-5 Screening Personality Questionnaire, SCID-5 Personality Disorders, and Personality Assessment Inventory). 24 , 34 - 36
Quiz Ref ID The primary outcome measure was the GRID-HAMD, 37 a version of the 17-item Hamilton Depression Rating Scale that has high reliability and validity. 26 The GRID-HAMD was administered by blinded clinician raters via telephone at baseline and at postrandomization weeks 5 and 8 for participants in the delayed treatment group and at the weeks 1 and 4 follow-up visits after the second psilocybin session for participants in both the immediate treatment and delayed treatment groups. The primary between-group end point comparison was at weeks 5 and 8 between the immediate treatment and delayed treatment groups ( Figure 2 ). The primary within-group end point comparison was between baseline and weeks 1 and 4 postsession 2 follow-up visits in both groups.
Severity of depression was assessed using the total GRID-HAMD score (0-7: no depression; 8-16: mild depression; 17-23: moderate depression; ≥24: severe depression). 38 A clinically significant response was defined as 50% or greater decrease from baseline; symptom remission was defined as a score of 7 or lower. The GRID-HAMD assessment was audiorecorded to examine interrater reliability (eMethods in Supplement 2 ). Interrater reliability for all depression assessments (through postsession week 4) was 85%. Rapid and sustained antidepressant effects were examined at baseline; at day 1 and week 1 of postsession-1 follow-up; and at day 1, week 1, and week 4 postsession-2 follow-up using the Quick Inventory of Depressive Symptomatology–Self-Report (QIDS-SR; score range: 0-27, with higher scores indicating very severe depression). 39
Descriptions of secondary outcome measures and timing of assessment are provided in the eMethods in Supplement 2 . Secondary outcome measures for depressive symptoms were the Beck Depression Inventory II (score range: 0-63, with higher scores indicating severe depression) 40 and the 9-item Patient Health Questionnaire (score range: 0-27, with higher scores indicating severe depression). 41 The Columbia-Suicide Severity Rating Scale (severity of ideation subscale score range: 0-5, with higher scores indicating presence of ideation with at least some intent to die) 42 , 43 was completed at every visit to assess for potentially worsening suicidal ideation throughout the trial. Anxiety symptoms were measured using the clinician-administered Hamilton Anxiety Rating Scale (score range: 0-56, with higher scores indicating severe anxiety) 44 and the State-Trait Anxiety Index (score range: 0-80, with higher scores indicating greater anxiety). 45 Blood pressure and heart rate were examined before and during the psilocybin sessions.
Data analysis was conducted on participants who completed the intervention (evaluable population). A previous study of psilocybin 16 found a large effect of a high psilocybin dose (compared with a low dose) on reducing GRID-HAMD scores (Cohen d = 1.30). Assuming a similar large effect size with 24 participants, nearly 100% power was calculated to detect a statistically significant effect of psilocybin on change in depressive symptoms.
No primary outcome data were missing. Descriptive statistics for demographic and background characteristics for all study variables were calculated and compared between study conditions using a 2-sample t test for continuous variables and a χ 2 test for all remaining variables. A repeated-measures analysis of variance with time (baseline, week 5, and week 8) and condition (immediate treatment and delayed treatment) as factors was used to examine changes in the primary depression outcome (GRID-HAMD score).
Follow-up planned comparisons included independent samples t tests to compare week 1 with week 4 GRID-HAMD scores in the immediate treatment condition group (corresponding to the week 5 and week 8 time points in the delayed treatment condition group). Within-participant (n = 24) treatment effect was examined using t tests comparing GRID-HAMD scores at baseline with scores at week 1 and week 4 postsession-2 follow-up. Rapid and sustained antidepressant effects were examined using t tests comparing QIDS-SR scores between baseline and day 1 postsession-1 and between baseline and week 4 postsession-2 follow-up. Effect sizes for the independent samples t tests were calculated using the Cohen d statistic, and effect sizes for the repeated-measures analysis of variance were calculated using the partial eta squared (η p 2 ) statistic. Further primary outcomes included a descriptive analysis of the percentage of participants who met the criterion for clinically significant response and remission in the sample.
All statistical tests used a P < .05 to determine statistical significance. Data analysis was conducted from July 1, 2019, to July 31, 2020, using SPSS, version 25 (IBM). 46 Data analysis plans for secondary outcomes are reported in the eMethods in Supplement 2 .
A total of 27 participants were randomized, of whom 24 (89%) completed the intervention as well as the postsession assessments at weeks 1 and 4; specifically, 13 were randomized to the immediate treatment group and 11 to the delayed treatment group ( Figure 1 ). The Table shows the demographic characteristics for the 24 participants, among whom were 16 women (67%) and 8 men (33%), with a mean (SD) age of 39.8 (12.2) years and a mean (SD) baseline GRID-HAMD score of 22.8 (3.9). An examination of the differences in stratification variables as a function of the treatment condition indicated no statistically significant differences between conditions (mean [SD] months in current major depressive episode: immediate treatment, 25.9 [22.4]; delayed treatment, 22.6 [22.5]; P = .39) ( Table ).
A statistically significant time by condition interaction effect on GRID-HAMD was found (η p 2 = 0.57; 90% CI, 0.38-0.66; P < .001) ( Figure 3 ).
Follow-up independent samples t tests revealed significantly lower depression scores in the immediate treatment condition at weeks 1 and 4 postsession-2 follow-up compared with the corresponding time points (weeks 5 and 8) in the delayed treatment condition before psilocybin treatment. In the immediate treatment group, the mean (SD) GRID-HAMD scores were 22.9 (3.6) at baseline, 8.0 (7.1) at week 5, and 8.5 (5.7) at week 8. In the delayed treatment group, the mean (SD) GRID-HAMD scores were 22.5 (4.4) at baseline, 23.8 (5.4) at week 5, and 23.5 (6.0) at week 8. The effect sizes were large at week 5 (Cohen d = 2.5; 95% CI, 1.4-3.5; P < .001) and at week 8 (Cohen d = 2.6; 95% CI, 1.5-3.7; P < .001) (eTables 1-3 and eResults in Supplement 2 ).
Quiz Ref ID After the psilocybin session, 17 participants (71%) at week 1 and 17 participants (71%) at week 4 had a clinically significant response to the intervention (≥50% reduction in GRID-HAMD score), and 14 participants (58%) at week 1 and 13 participants (54%) at week 4 met the criteria for remission of depression (≤7 GRID-HAMD score). Within-participant t tests showed statistically significant decreases in GRID-HAMD scores among participants from baseline to week 1 (Cohen d = 2.3; 95% CI, 1.5-3.1; P < .001) and week 4 (Cohen d = 2.3; 95% CI, 1.5-3.1; P < .001) ( Figure 4 ). The QIDS-SR measure of depression, which was assessed more frequently, showed a rapid, large decrease in mean (SD) depression score among participants from baseline to day 1 after psilocybin session 1 (16.7 [3.5] vs 6.3 [4.4]; Cohen d = 2.6; 95% CI, 1.8-3.5; P < .001). This substantial decrease remained through week 4 after session 2 (6.0 [5.7]; Cohen d = 2.3; 95% CI, 1.5-3.0; P < .001) (eFigure 1 in Supplement 2 ).
All secondary depression and anxiety outcomes showed a similar pattern of results as the primary depression outcomes, with statistically significant differences between conditions and across both conditions after entry into the active intervention period (eTables 1 to 3 and eFigures 1 to 8 in Supplement 2 ). For example, statistically significant treatment condition effects were found on self-reported depression (Beck Depression Inventory II and Patient Health Questionnaire–9) and clinician-administered anxiety (Hamilton Anxiety Rating Scale) measures. Overall, suicidal ideation was low and trended lower after enrollment in both groups (eFigure 9 in Supplement 2 ).
Participant and facilitator rated intensity of acute psilocybin effects are provided in eTables 4-6 in Supplement 2 . There were no serious adverse events in this trial. A transient increase in blood pressure that exceeded the protocol criteria for more frequent assessment (ie, diastolic blood pressure >100 mm Hg) occurred during 1 session, but no medical intervention was needed, and the blood pressure level remained within predetermined safety parameters and resolved spontaneously during the session (eTable 7 in Supplement 2 ). Other nonserious adverse effects, which occurred during the psilocybin administration, that were reported by participants after completing at least one-half of the psilocybin sessions included challenging emotional (eg, fear and sadness) and physical (eg, feeling body shake or tremble) experiences (eTable 8 in Supplement 2 ). Mild to moderate transient headache was reported during 16 of 48 sessions (33%) and after the subjective psilocybin effects had subsided after 14 of 48 sessions (29%). Other adverse events are reported in eTables 8 and 9 in Supplement 2 , and initiation of antidepressants or psychotherapy is reported in eTable 10 in Supplement 2 .
This randomized clinical trial documented the substantial rapid and enduring antidepressant effects of psilocybin-assisted therapy among patients with MDD. Although the rapid antidepressant effects of psilocybin are similar to those reported with ketamine, 10 , 11 the therapeutic effects are different: ketamine effects typically last for a few days to 2 weeks, whereas the current study showed that clinically significant antidepressant response to psilocybin therapy persisted for at least 4 weeks, with 71% of the participants continuing to show a clinically significant response (≥50% reduction in GRID-HAMD score) at week 4 of follow-up. Furthermore, psilocybin was found to have low potential for addiction 22 and a minimal adverse event profile, 22 , 23 suggesting therapeutic advantages with less risk for associated problems than ketamine. 12 The present findings in patients with MDD are consistent with results of studies that reported on the effectiveness of psilocybin-assisted therapy in producing antidepressant effects among patients with cancer who had psychological distress 16 , 17 , 47 and a small open-label study of patients with treatment-resistant depression. 18
The mounting evidence of the use of psilocybin as an adjunct to treatment of a variety of psychiatric conditions (eg, depression, 16 - 18 tobacco use disorder, 48 and alcohol use disorder 49 ) suggests a transdiagnostic mechanism of action. In several studies in patients 16 - 18 , 49 - 51 and in healthy volunteers, 32 , 52 the intensity of mystical-type experiences reported after psilocybin sessions was associated with favorable outcomes. Furthermore, cross-sectional studies have suggested that mystical-type and psychologically insightful experiences during a psychedelic session predict positive therapeutic effects. 53 - 55 Consistent with these previous studies, the current trial showed that psilocybin-occasioned mystical-type, personally meaningful, and insightful experiences were associated with decreases in depression at 4 weeks (eResults in Supplement 2 ). Furthermore, a recent report suggested that psilocybin may decrease negative affect and the neural correlates of negative affect, 56 which may be a mechanism underlying transdiagnostic efficacy. Taken together, these findings suggest that further studies into psychological and neural mechanisms across different psychiatric conditions are warranted.
The present trial showed that psilocybin administered in the context of supportive psychotherapy (approximately 11 hours) produced large, rapid, and sustained antidepressant effects. The effect sizes reported in this study were approximately 2.5 times greater than the effect sizes found in psychotherapy 57 and more than 4 times greater than the effect sizes found in psychopharmacological depression treatment studies. 58 These findings are consistent with literature that showed that combined pharmacotherapy and psychotherapy were more efficacious in the treatment of MDD than either intervention alone. 59 - 61 Furthermore, given that psilocybin was associated with nonserious adverse effects that were frequently reported as mild-to-moderate headache and challenging emotions that were limited to the time of sessions (eTables 8 and 9 in Supplement 2 ), this intervention may be more acceptable to patients than widely prescribed antidepressant medications that confer substantially more problematic effects (eg, suicidal ideation, decrease in sexual drive, and weight gain). The effectiveness of psilocybin therapy after a single or only a few administrations represents another substantial advantage over commonly used antidepressants that require daily administration.
This study has some strengths. It had a randomized design and used GRID-HAMD as the primary outcome measure that was assessed by blinded clinician raters. The delayed treatment condition controlled for the possible effects of having been accepted into the trial and for the passage of time between screening and initial follow-up assessments. However, the delayed treatment condition did not control for other aspects of psilocybin administration, such as preparation and rapport building, postsession integration meetings, or expectancy effects. Although placebo and active treatment controlled designs are widely used in therapeutic trials, 62 they too have limitations owing to the highly discriminable effects of psilocybin.
Quiz Ref ID This study has some other limitations. It had a short-term follow-up, a small sample that was predominantly composed of White non-Hispanic participants, and included participants with low risk of suicide and moderately severe depression. Further research with larger and more diverse samples, longer-term follow-up, and a placebo control is needed to better ascertain the safety (eg, abuse potential of psilocybin, suicide risk, and emergence of psychosis) and efficacy of this intervention among patients with MDD. Another limitation is the psychotherapy approach 31 that involved session facilitators from a variety of professional disciplines (eg, social work, psychology, psychiatry) and session facilitators without formal clinical training (eg, research assistants and clinical trainees). The type of psychotherapy offered and the characteristics of therapists should be explored in future studies.
Results of this randomized clinical trial demonstrated the efficacy of psilocybin-assisted therapy in producing large, rapid, and sustained antidepressant effects among patients with MDD. These data expand the findings of previous studies involving patients with cancer and depression as well as patients with treatment-resistant depression by suggesting that psilocybin may be effective in the much larger population of MDD. Further studies are needed with active treatment or placebo controls and in larger and more diverse populations.
Accepted for Publication: July 31, 2020.
Published Online: November 4, 2020. doi:10.1001/jamapsychiatry.2020.3285
Correction: This article was corrected on February 10, 2021, to fix errors in the Abstract Results and Results section.
Open Access: This is an open access article distributed under the terms of the CC-BY License . © 2020 Davis AK et al. JAMA Psychiatry .
Corresponding Authors: Alan K. Davis, PhD ( [email protected] ), and Roland R. Griffiths, PhD ( [email protected] ), Center for Psychedelic and Consciousness Research, Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, 5510 Nathan Shock Drive, Baltimore, MD 21224.
Author Contributions: Drs Davis and Griffiths had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Davis, Barrett, May, Cosimano, Johnson, Griffiths.
Acquisition, analysis, or interpretation of data: Davis, Barrett, May, Sepeda, Johnson, Finan, Griffiths.
Drafting of the manuscript: Davis, Barrett, May, Cosimano, Sepeda, Griffiths.
Critical revision of the manuscript for important intellectual content: Davis, Barrett, May, Sepeda, Johnson, Finan, Griffiths.
Statistical analysis: Davis, Griffiths.
Obtained funding: Barrett, Griffiths.
Administrative, technical, or material support: Davis, Barrett, May, Cosimano, Sepeda, Finan, Griffiths.
Supervision: Davis, Barrett, May, Cosimano, Johnson, Griffiths.
Conflict of Interest Disclosures: Dr Davis reported being a board member at Source Research Foundation. Dr Johnson reported receiving grants from Heffter Research Institute outside the submitted work and personal fees as a consultant and/or advisory board member from Beckley Psychedelics Ltd, Entheogen Biomedical Corp, Field Trip Psychedelics Inc, Mind Medicine Inc, and Otsuka Pharmaceutical Development & Commercialization Inc. Dr Griffiths reported being a board member at Heffter Research Institute and receiving grants from Heffter Research Institute outside the submitted work. No other disclosures were reported.
Funding/Support: This study was funded in part by a crowd-sourced funding campaign organized by Tim Ferriss; a grant from the Riverstyx Foundation; and grants from Tim Ferriss, Matt Mullenweg, Craig Nerenberg, Blake Mycoskie, and the Steven and Alexandra Cohen Foundation. Drs Davis and May were supported by postdoctoral training grant T32DA07209 from NIDA. Dr Finan was supported by grant K23DA035915 from NIDA. Drs Griffiths and Johnson were partially supported by grant R01DA03889 from NIDA. The Center for Psychedelic and Consciousness Research is funded by the Steven and Alexandra Cohen Foundation and has received support from Tim Ferriss, Matt Mullenweg, Craig Nerenberg, and Blake Mycoskie.
Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Additional Contributions: Annie Umbricht, MD, and Eric Strain, MD, provided medical oversight during the study sessions. Jessiy Salwen, PhD, and Mary Bailes, LCPC, served as blinded clinician raters. Natalie Gukasyan, MD; Laura Doyle, BA; John Clifton, BS; Kasey Cox, MS; and Rhiannon Mayhugh, PhD, facilitated the intervention sessions. These individuals, from Johns Hopkins University, received no additional compensation, outside of their usual salary, for their contributions.
Data Sharing Statement: See Supplement 3 .
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Sara, a 35-year-old married female. Sara was referred to treatment after having a stillbirth. Sara showed symptoms of grief, or complicated bereavement, and was diagnosed with major depression, recurrent. The clinician recommended interpersonal psychotherapy (IPT) for a duration of 12 weeks. Bleiberg, K.L., & Markowitz, J.C. (2008).
bject case study design was used in which pre and post-assessment was carried out. Cognitive. behaviour casework intervention was used in dealing with a client with depression. Through an in-depth case study using face to face interview with the client and f. mily members the detailed clinical and social history of the clients was ass.
Strengths and Assets: bright, attractive, personable, cooperative, collaborative, many good social skills Treatment Plan Goals (measures): Reduce symptoms of depression and anxiety (BDI, BAI). To feel more comfortable and less pressured in relationships, less guilty. To be less dependent in relationships.
The severity of depressive episodes was measured using the Hamilton Depression Scale (HAM-D). Themes of guilt and shame were measured by using the State of Guilt and Shame Scale (SSGS). This case study was presented as a poster abstract at the 'RCPsych Faculty of General Adult Psychiatry Annual Conference 2021.'
Sarah's case study highlights several important lessons about depression and its treatment: 1. Early intervention is crucial: Sarah's initial reluctance to seek help led to a prolongation of her symptoms. Recognizing and addressing mental health concerns early can prevent the condition from worsening. 2.
In a recent study by Midgley and colleagues (2015), a British sample of 77 adolescents (11-17 years) who had been diagnosed with depression and were entering outpatient psychotherapy, were interviewed about the individual experience of depression as part of a large randomized controlled trial, the Improving Mood With Psychoanalytic and ...
the case study had a therapist who was a doctoral level graduate student in clinical psychology trained in CBT who received weekly supervision from a licensed clinical psychologist with a Ph.D. Qualitative data for this case study were analyzed by reviewing progress notes and video recordings of therapy sessions. SESSIONS 1-4
Diagnosis of depression can be made using the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) or the 10th revision of the International Statistical Classification of Disease and Related Health Problems (ICD-10). 5 (Refer to Appendix 3 and 4, pages 73-76 in CPG.) 6,7
Chapter 4 covers the treatment of depression, and discusses popular myths regarding depression, its frequency, characteristics and diagnosis, and includes case studies, assessment, case conceptualization, intervention development and course of treatment, problems that may arise in therapy, ethical considerations, common mistakes in the course ...
Depression from an evolutionary perspective. Because of the universality and prevalence of mental illness, attempts have been made in Evolutionary Psychology to explain the possible functions of utility of some symptoms 23-25.From this perspective, some mental disorders are seen as having present or past fitness advantages 26 and therefore might have been naturally selected (e.g., mild and ...
depression (e.g., avoidance, difficulty concentrating and making decisions, and fatigue) as additional signs of incompetence. Once he became depressed, he interpreted many of his experiences through the lens of his core belief of incompetence or failure. Three of these situations are noted at the bottom of the Case Conceptualization Diagram.
A case study of person with depression: a cognitive behavioural case work approach. September 2020. International Journal of Indian Psychology 8 (3):620-630. 8 (3):620-630. DOI: 10.25215/0803.072 ...
have contributed to depression and referred cli-ents for appropriate concurrent medical treat-ment, if necessary. CASE STUDY Background Information The following section presents the treatment of Mark, a 43-year-old man with a long history of depression, who sought treatment after the end of his second marriage. Mark was in treatment
e. R. Cognitive Behavior Therapy for Depression: A Case Report. Ara J*. Department of Clinical Psychology, Arts Building, Dhaka University, Bangladesh. Abstract. Depression is expected to become ...
Rowan Digital Works
The adolescent chosen for the case study had a therapist who was a doctoral level graduate student in clinical psychology trained in CBT who received weekly supervision from a licensed clinical psychologist with a Ph.D. Qualitative data for this case study were analyzed by reviewing progress notes and video recordings of therapy sessions.
A unified protocol based on empirically-supported methods of PDT in depression may contribute to solve these problems Systematic search for randomized controlled trials fulfilling the following criteria: (a) individual psychodynamic therapy (PDT) of depressive disorders, (b) treatment manuals or manual-like guidelines, (c) PDT proved to be ...
This case study used single case experimental design methodology to examine the ... depression: the case for augmented, individually tailored cognitive ... Morley S. Single Case Methods in Clinical Psychology: A Practical Guide. Routledge. 2018. ISBN: 978 -1 138 21149 0 39. Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief
Studies on depression have increased significantly over the past few decades. However, the literature remains fragmented and the interpretation of heterogeneous findings across studies and between fields is difficult. The cross-pollination of ideas between disciplines, such as genetics, neurology, immunology, and psychology, is limited.
Nonchronic Depression In the case study that follows, we describe the course of treatment for a nonchronically de-pressed woman seen at our center. Through the case study, we illustrate many of the concepts described earlier in this chapter, including elici-tation of automatic thoughts, the cognitive triad of depression, collaborative empiricism,
Persistent depressive disorder, anorexia and obsessive-compulsive disorder are each psychopathologic entities with suicidal risk. When they appear together it is a must that a multidisciplinary ...
Key points. Depression is a multi-faceted condition affecting every aspect of life, requiring personalized treatment. Depression's causes can be biological, psychological, and social; it is not ...
Depression is extreme sadness or despair that lasts more than days. It interferes with the activities of daily life and can cause physical symptoms such as pain, weight loss or gain, sleeping pattern disruptions, or lack of energy. People with depression may also experience an inability to concentrate, feelings of worthlessness or excessive ...
The effect sizes reported in this study were approximately 2.5 times greater than the effect sizes found in psychotherapy 57 and more than 4 times greater than the effect sizes found in psychopharmacological depression treatment studies. 58 These findings are consistent with literature that showed that combined pharmacotherapy and psychotherapy ...
Even in conditions like postpartum depression and generalised anxiety disorder, where antidepressants are the primary treatment, this case study demonstrates how innovative approaches can pave new paths for psychotherapeutic exploration. It also challenges the notion of therapeutic stability as an absolute requirement for progress in psychotherapy.