From the Editor

She was distressed by the voices and the paranoid thoughts. Many nights, my patient could barely sleep. She had tried several medications without much improvement. Is there a role for psychological interventions? Would CBT help? What is the evidence for this population?

In the first selection, Nurul Husna Salahuddin (of the Technical University of Munich) and co-authors attempt to answer these questions in a new systematic review and network meta-analysis, just published in Lancet Psychiatry. The analyzed 52 RCTs with 5 034 participants. “We provide robust findings that CBTp can reduce the overall symptoms of patients with treatment-resistant schizophrenia, and therefore clinicians can prioritise this intervention in their clinical practice.” We consider the paper and its clinical implications.

In the second selection from JAMA Network Open, Sarah C. Leighton (of the University of Arizona) and her co-authors describe a study involving service dogs for those with PTSD. In a nonrandomized controlled trial involving 156 military members and veterans, they examined outcomes after three months. “[C]ompared with usual care alone, partnership with a trained psychiatric service dog was associated with lower PTSD symptom severity and higher psychosocial functioning in veterans.”

Finally, we explore the latest news with recent articles from The Guardian, the Ottawa Citizen, and The New York Times. Among the topics: “honest” obituaries and the opioid crisis, antidepressants and withdrawal, and care for pregnant women with substance problems.


Selection 1: “Psychological and psychosocial interventions for treatment-resistant schizophrenia: a systematic review and network meta-analysis”

Nurul Husna Salahuddin, Alexandra Schütz, Gabi Pitschel-Walz, et al.

The Lancet Psychiatry, 4 July 2024  Online First

Schizophrenia is a chronic and serious mental illness affecting almost 24 million people worldwide, characterised by positive, negative, affective, and cognitive symptoms leading to serious functional disability. Pharmacological interventions with antipsychotics have been the mainstay of treatment since their introduction in the 1950s. However, antipsychotics are not always effective in treating the symptoms of the illness…

To the best of our knowledge, only two small reviews on psychological interventions have been conducted in patients with treatment-resistant schizophrenia, but they were restricted to cognitive behavioural therapy (CBT) and used a simple pairwise meta-analysis. As a result, the current evidence does not answer the question of which psychological treatments are likely to be the best in the different outcome parameters (eg, symptoms of schizophrenia or functioning) for treatment-resistant schizophrenia.

Here’s what they did:

  • They conducted a systematic review and network meta-analysis after searching for published and unpublished randomized controlled trials (RCTs) and “included all randomised controlled trials (RCTs) that compared psychological or psychosocial interventions in adults with a diagnosis of schizophrenia or related disorders.”
  • They drew on several databases, including PubMed.
  • “No restrictions in terms of gender, ethnicity, language, country, or setting were applied.”
  • The primary outcome: “overall symptoms of schizophrenia measured by validated rating scales at end of treatment.”

Here’s what they found: 

  • They screened more than 30 000 records, and retrieved and assessed 5 762 full-text articles. Many were excluded, leaving 222 records (60 studies) for the network meta-analysis and 200 for the quantitative synthesis (52 RCTs).
  • Demographics and illness experience. Most participants were men (66.8%) with a mean age of 38 years. Most were moderately ill, and the mean duration of illness was 12.96 years.
  • Risk of bias. The risk of bias was judged to be low for two studies, moderate for 21 studies, and high for eight studies.
  • Network meta-analysis. Of these, 52 RCTs comparing 20 psychological and psychosocial interventions provided data for the NMA. “Cognitive behavioural therapy for psychosis (CBTp; SMD –0·22… 35 trials), virtual reality intervention (SMD –0·41… four trials), integrated intervention (SMD –0·70… three trials), and music therapy (SMD –1·27… one study) were more efficacious than standard care in reducing overall symptoms.”

A few thoughts:

1. This is a good study, drawing on RCTs, with practical implications and published in a major journal.

2. The main finding in five words: there is evidence for CBT.

3. To offer more details: “We found that CBTp, virtual reality interventions, integrated intervention, and music therapy were superior to treatment as usual in reducing overall symptoms of schizophrenia in participants with treatment-resistant schizophrenia.”

4. Good news. There are clear clinical implications.

5. But the results are hardly amazing and somewhat of a mixed bag. Yes, CBT reduced positive symptoms and improved quality of life, but it had a less clear effect on negative symptoms and didn’t improve overall functionality. 

6. And there are clear problems with the study. The definition of treatment-resistant schizophrenia varied (including non-response stated and no response to two meds). As the authors note: “the descriptions of the treatment-resistant schizophrenia population in the studies were sometimes poor, and less strict than observed in studies investigating drugs in the same population.” (In fact, they go further: “We found only one RCT that applied the comprehensive treatment-resistant schizophrenia definition recommended by Kane and colleagues, but no usable data were reported.”)

7. The big strength of this paper – the numerous interventions studied – is also its weakness. Consider: they looked at 20 interventions in 52 studies. Needless to say, the number of studies for individual interventions was, then, small. (Music therapy was analyzed in just one study.)

8. The authors conclude that “clinicians can prioritise this intervention.” Are they overly enthusiastic?

The full Lancet Psych paper can be found here:

Selection 2: “Service Dogs for Veterans and Military Members With Posttraumatic Stress Disorder: A Nonrandomized Controlled Trial”

Sarah C. Leighton, Kerri E. Rodriguez, Clare L. Jensen, et al.

JAMA Network Open, 4 June 2024

Posttraumatic stress disorder (PTSD) is a pressing concern for military members and veterans (hereafter, veterans), with an estimated prevalence of 23% among those with post-9/11 service. Posttraumatic stress disorder is characterized by symptoms of intrusion, avoidance of trauma reminders, adverse alterations in cognition and mood, and increased arousal and reactivity…

Currently, PTSD remains difficult to treat. Existing evidence-based treatments for PTSD are effective for some individuals, but uptake and retention are limited. Veterans are increasingly seeking out psychiatric service dogs (hereafter, service dogs) as complementary interventions. However, the effectiveness of service dogs remains understudied. Service dogs, referred to as assistance dogs internationally, are defined under US federal law as ‘dogs that are individually trained to do work or perform tasks for people with disabilities.’ Preliminary evidence indicates that service dog partnerships are associated with meaningful improvements in self-reported PTSD symptoms for veterans with PTSD. However, only 1 clinical trial on their efficacy has been conducted to date, which compared emotional support dogs to service dogs, precluding conclusions about service dogs compared with usual care alone.

So begins a paper by Leighton et al.

Here’s what they did:

  • They conducted a nonrandomized controlled trial with veterans who had a PTSD diagnosis.
  • “Veterans were recruited using the database of an accredited nonprofit service dog organization with constituents throughout the US.”
  • The intervention: “Participants allocated to the intervention group received a psychiatric service dog for PTSD, whereas those allocated to the control group remained on the waiting list based on the date of application submitted to the service dog organization.” The veterans in the intervention group were partnered with service dogs during a 3-week, onsite, group class; the curriculum included 40 hours per week of instruction in service dog care, training, and interaction.
  • Primary outcome: “PTSD symptom severity, depression, and anxiety after 3 months.” They used two scales: the PTSD Checklist for DSM-5 (PCL-5, which is self-reported) and the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5).

Here’s what they found:

  • 200 veterans were screened with 170 deemed eligible, though some were then excluded. In total, 156 were followed (75 in the control group and 81 in the intervention group).
  • Demographics and burden of illness. The mean age was 37.6 years and most participants were male (75%) and White (76%). Many (42%) had pet dogs at baseline. The intervention and control groups had similar PCL-5 scores at baseline.
  • Dogs. In terms of the dogs, “breeds were predominantly mixed (59%), and the most common pure breed was a Labrador retriever (22%).”
  • Outcomes. “Participants in the intervention group reported significantly lower PTSD symptom severity after 3 months compared with participants in the control group, based on the PCL-5 (OR, 0.22…difference in means, −11.5…) and the CAPS-5 (OR, 0.21 … difference in means, −7.0…) outcomes.” Secondary outcomes: Measures of depression, anxiety, and social isolation were lower in those who received dogs.
  • Adverse events. There were more adverse events in the control group than in the intervention group (4 versus 6).

A few thoughts:

1. This is an interesting study which features data on an animal intervention.

2. The main finding in two words: dogs helped.

3. There is something compelling, even charming, about this study. Needless to say, the publication has received much media attention. For the record, USA Today had the best headline: “4-legged lifesavers: Service dogs are working wonders for veterans with PTSD, study shows.”

4. There was significant training of the dogs. “Service dogs received at least 60 hours of professional training and passed a final obedience and specialized skill proficiency test. Specialized PTSD-related skills included interrupt or alert to anxiety, calm or comfort anxiety, block (create space), cover (watch back), and make a friend (social greeting).”

5. And while the study is compelling, there are problems. Start here: it wasn’t randomized. As the authors note: “Participants received service dogs based on their position on the waiting list, which was determined by their application date.” 

6. Moreover, the veterans had self-selected: they had all applied for a service dog. Would other veterans – including those cooler to animals – have shown the same benefits?

The full JAMA Netw Open paper can be found here:

In the News

Part of an occasional series.

“He lost his father and brother to fentanyl, so he wrote ‘honest’ death notices” 

Andrew Duffy

Ottawa Citizen, 27 June 2024

“Matthew Larventz owns a uniquely unhappy place in the tragedy that is Ottawa’s opioid epidemic.

“The 34-year-old Ottawa lobbyist has lost both his father, James, and his brother, Christopher, to fentanyl overdoses in the past seven years.

“‘I have lost half my nuclear family to this crisis,’ he says.”

The article discusses his decision to be “honest” about these deaths. In the obituary of his father, who died in 2022 of a fentanyl overdose, Larventz wrote bluntly about the struggles with opioids. He calls the decision “cathartic” and hopes that it will help “to end the stigma of addiction.” He used a similar approach after the recent death of his brother. 

The article, written by journalist Andrew Duffy, notes that 450 people have died from opioids in Ottawa over the past three years, yet only a handful of notices mentioned substance. 

People with substance problems face ongoing stigma – even in death.

“The myth that antidepressants are addictive has been debunked – they are a vital tool in psychiatry”

Carmine M. Pariante

The Guardian, 8 June 2024

“I have been prescribing antidepressants since 1991. Like most medications, they are imperfect tools: they have side-effects and don’t work for everybody. Some patients report negative effects, or that their depression does not improve, and they may require changing to a different antidepressant. For those they do help, antidepressants undoubtedly improve depression and reduce the risk of suicide.

“Very rarely, in my clinical practice, do patients complain that they cannot stop their medication because of the symptoms when they try. Unpleasant physical or emotional experiences for a few days or a couple of weeks after stopping antidepressants, yes: dizziness, headache, nausea, insomnia, irritability, vivid dreams, electricity-like sensations or rapid mood swings. But patients who could not stop the antidepressant because of these symptoms? In my 33 years of clinical practice, I can recall them on the fingers of one hand.”

Dr. Pariante, a psychiatrist affiliated with King’s College London, writes about concerns voiced by some that antidepressants are addictive and that efforts to stop these meds are met with severe withdrawal symptoms. He draws on his clinical experience and then delves into the new Henssler et al. study (analyzed in last week’s Reading), finding that few patients have severe withdrawal symptoms. “People will make different decisions through an informed discussion with their doctor… Many factors will influence these decisions, but at least the now-debunked myth that antidepressants are addictive will no longer be one of these factors.”

The essay is well written. Sharing it with some patients may help better inform their decision to start an antidepressant trial.

“Pregnant, Addicted and Fighting the Pull of Drugs”

Jan Hoffman

The New York Times, 16 June 2024

“Kim Short waited in the doctor’s exam room on an icy day in February, exhausted from the first trimester of pregnancy and trembling in withdrawal from methamphetamine, alcohol, Xanax and Klonopin.

“She stared at the floor, her black hair curtaining face tattoos of a dagger and stitches, memorials to friends dead from overdose. Inky wings of eyeliner rimmed her eyes.

“This was Kim’s second pregnancy with the Great Moms clinic at the Corewell Health Medical Center in Grand Rapids…”

So begins a long essay about Kim and her journey – the sobriety she achieved, her relapse after the birth of her child, her work to have a healthy second pregnancy. The article describes at length her physician, the clinic’s founder, Dr. Cara Poland, who specializes in addiction medicine. Dr. Poland is persistent in her work, perhaps because of her own experiences; her brother died at 24 after struggling with depression and alcohol use disorder. “I’ve yet to meet a person who doesn’t try to change something about their health because they’re pregnant… It just happens the thing my patients are trying to change is their drug use.”

The essay is moving, and Dr. Poland’s passion is inspiring.

Reading of the Week. Every week I pick articles and papers from the world of Psychiatry.