CCPR: Dr. Rynn, your work is focused on the treatment of children with anxiety disorders. What can you tell us about generalized anxiety disorder? Is this a big problem among children and adolescents?

Dr. Rynn: Anxiety disorders, in general, for children and adolescents, can be a very big problem. A big issue is that anxiety disorders are often not the first diagnoses considered and they are often overlooked. During my time of working with anxiety disorders, I am always struck by how long a child suffers before getting the diagnosis and targeted treatment.

CCPR: So what should tip clinicians off that they should be thinking “anxiety disorder”?

Dr. Rynn: It depends on the child, but for some children it may seem like more of a medical problem because they are having multiple somatic complaints, like headaches, gastrointestinal problems and so forth. Other children with anxiety disorders may behave in a very oppositional manner, causing problems for them in school and with family members. In my experience this can be particularly true of boys.

CCPR: So a kid may seem aggressive or like he has ADHD, when in fact it’s anxiety.

Dr. Rynn: Yes. You might have a boy where the situation escalates to the point he throws the chair across the classroom because he doesn’t like to be called on and/or be asked to talk in front of people. Sometimes these children can’t verbally describe the experiences that they are having—the anxiety they are feeling—and so some of the behaviors may be viewed as a different disorder. 

CCPR: Depression and anxiety are so often comorbid. Do you have any good ways of separating out kids who are fundamentally depressed and have comorbid anxiety, versus kids who are fundamentally anxious and have comorbid depression?

Dr. Rynn: I wish I had a great method, but really the best thing is a very careful history and to be sure to get information from all the adults who are in that child’s life. When a child is able to articulate what she is feeling—does she isolate herself from other kids because she’s sad or because she’s shy or afraid of saying something stupid—we can better understand what is driving the behavior. 

CCPR: Why is it with kids that it seems that they either come in with no anxiety disorders or a bunch of them, not just one?

Dr. Rynn: We call this the anxiety triad, which includes separation anxiety, social phobia, and generalized anxiety disorder together. They exhibit strong association comorbidly over time. Fortunately, they respond similarly to the same treatments, like cognitive behavioral therapy (CBT) and medication treatment. When you look at some of the major clinical trials that have been done on childhood anxiety, you see that close to half of the sample will have, in addition to the primary anxiety diagnosis, another diagnosis, and often a secondary anxiety diagnosis (Kendall, PC et al, J Anx Dis 2010;24:360–365).

CCPR: What is the first-line treatment for generalized anxiety disorder?

Dr. Rynn: In terms of psychotherapy, CBT is considered a first-line treatment option. Numerous studies have shown CBT is effective for pediatric GAD. The Child-Adolescent Anxiety Multimodal Study (CAMS) is the largest pediatric anxiety study to date. It compared either 1) CBT alone, 2) sertraline (Zoloft) alone, 3) sertraline in combination with CBT, or 4) pill placebo for the anxiety triad. All three active treatments clearly separated from pill placebo. Among the active groups, the combined treatment showedan 80.7% response rate; 59.7% for CBT alone; and sertraline alone, 54.9% (Walkup JT et al, New Engl J Med 2008; 359(26):2753– 66). So you can see that combined treatment—CBT plus medication—is very successful; however the two monotherapies were efficacious as well.

CCPR: You have done some work on attachment-based CBT. Can you tell us about that?

Dr. Rynn: I had the opportunity to work with colleagues (Drs. Siqueland and Diamond) at the Department of Psychiatry at the University of Pennsylvania who were looking at a modified combination of cognitive behavioral (CBT) and attachment-based family therapy (ABFT) in the context of working with the parent/child relationship for anxiety disorders. When a child has a problem with anxiety, there are often other family members stuggling with the child’s symptoms of anxiety as well as their own (Siqueland L etal, J Anx Dis 2005;19:361–381). We also found that when parents have the disorder themselves and are untreated, our treatments don’t work as well.

CCPR: So this would be therapy for both the child’s anxiety and the parent’s?Dr. Rynn: Yes, by targeting the parent’s response to the child’s anxiety. It targets how families model management of the child’s anxiety in certain situations, and how these reponses may lead to the development and maintenance of childhood anxiety. addition, it examines how a family problem-solves stressful situations together, and how that may reinforce the anxiety symptoms that the child is experiencing. There are types of family patterns and responses that are not helpful to the anxious child, such as being overprotective, overcritical, not allowing children to experience failure, not allowing children to venture out on their own, or making children feel insecure about their abilities. This comes about partly because parents are experiencing so much anxiety on their own, including fear that the child will not succeed.

CCPR: What medications work for anxiety in kids?

Dr. Rynn: The first line of medications that we recommend is the serotonin reuptake inhibitors. A substantial number of studies show that they are safe and efficacious for the treatment of anxiety disorders. (For review see Rynn MA et al, Depression Anxiety 2011;28:76–87.) And other studies have examined and shown the efficacy of an SSRI and CBT (Pediatric OCD Treatment Study Team, JAMA 2004;292:1969–1976).

CCPR: What about SNRIs?

Dr. Rynn: There have been some studies looking at SNRIs—three looking at venlafaxine extended release (Effexor ER). Two of these had generalized anxiety disorder as the primary diagnosis. In one, there was a distinct separation between drug vs placebo.In the second, venlafaxine did not separate from placebo, but the placebo rate in the study was high (Rynn MA et al, Am J Psychiatry 2007;164(2):290–300). The third study was of social anxiety disorder, and again, there was a clear separation between the medication and the placebo (March JS et al, Biol Psychiatry 2007;62(10):1149–1154). So, yes, venlafaxine works. But it is not recommended as a first line of treatment because it also requires monitoring of vital signs.

CCPR: So you might reserve SNRIs for a child who has failed a trial of an SSRI.

Dr. Rynn: I think it is a compound to consider if a child has failed at least one trial of an SSRI, potentially even a second trial ofan SSRI because we have some evidence to suggest switching a child to another SSRI may produce a response (Research Unit on Pediatric Psychopharmacology Anxiety Study Group, J Child Adolesc Psychopharmacology 2002;12:175–188).

CCPR: What else do you recommend? What about benzodiazepines?

Dr. Rynn: I actually think benzodiazepines can be helpful for children with anxiety disorders, particularly for children who are suffering from significant physical symptoms. These are the children whose parents say, “He is grabbing the side of the door so I can’t get him out the door; he has stomach aches; the nurse is constantly calling me telling me to pick him up.” And there are times when the a psychotherapist will contact me saying, “The child is unable to do the psychotherapy piece because the he/she is so preoccupied with these physical symptoms that I can’t begin to start to teach any of the tools.” So for these children I will actually use benzodiazepines in the initial treatment phase.

CCPR: Which benzos in particular and at what dosages?

Dr. Rynn: Generally I use clonazepam (Klonopin) due to its long half-life and because there are different dosing options. Depending on the child, I may start with 0.25 mg, give a test dose in the morning, and have the parent call me to see how the child tolerated the dose. If it seems not to help, I increase to 0.5 and might use a couple of doses during the day as we are initiating treatment, whether it is cognitive behavioral therapy or starting the antidepressant. This is a helpful way to alleviate some of the suffering that the child and the family are experiencing.

CCPR: What about the problem of disinhibition on these medications?

Dr. Rynn: The few clinical trials of benzodiazepines show that there have been reports of activation or disinhibition (Rynn MA et al, Depression and Anxiety 2011;28:76–87). So you do need to watch for those side effects, but in my experience, it has not been a huge problem.

CCPR: What about some other agents? What would you say second-line medications are?

Dr. Rynn: If you do not have success after trying the SSRIs and then SNRIs, there are not a lot of data to support what is the best next option. Whenever possible CBT should be added if it has not already been instituted. Buspirone has some evidence, and I have had some children respond well to buspirone (Simeon J et al, J Child Adolesc Psychopharmacology 1994;4(3):159–170). The adult literature supports the combination of a benzodiazepine with the SSRI as another approach (Goddard AW et al, Arch Gen Psychiatry 2001;58:681–686).

CCPR: What else? How about clonidine?

Dr. Rynn: I have not used clonidine (Catapres) or guanfacine (Tenex), but there is off-label use for these compounds to treat anxiety sleep problems and the somatic symptoms. Children with anxiety have difficulty with focusing and this leads to difficulty in many areas. In the adult literature there is limited information about the use of these compounds to treat GAD and Panic Disorder (Hoehn-Saric R et al, Arch Gen Psychiatry 1981;38(11):1278–1282).

CCPR: Are there any meds you recommend we stay away from?

Dr. Rynn: I am aware of open label and case studies using mirtazapine (Remeron) for social anxiety disorder in children (Mrakotsky C et al, J Anxiety Dis 2008;22:88–97). I would not say to never use gabapentin (Neurontin) or pregabalin (Lyrica), but these compounds are not well-studied in children and I would be sure I exhausted all the treatments that have evidence to support their use. And then I would reassess to be sure I have the correct diagnosis and/or did not miss a comorbid diagnosis.

CCPR: Is there anything new on the horizon for treating anxiety disorders?

Dr. Rynn: I am hopeful as neuroscience advances that new medications will be developed from the identification of specificbrain targets and that might actually enhance psychotherapy through complimentary mechanisms. For example I think the work with D-cycloserine is very interesting. And in the field we now have preliminary data that it may work in pediatric OCD. A study was done with D-cycloserine used to enhance cognitive behavioral therapy for children and adolescents with OCDand the results provide evidence for the clinical benefit to this approach (Storch EA et al, Biol Psychiatry 2010;68:1073– 1076). However, a larger study needs to be completed. Also, D-cycloserine in combination with CBT has been looked atin adults with OCD, generalized anxiety disorder, and social phobia. All of these studies had different methods in usingthe D-cycloserine but the general approach was to give a D-cycloserine dose (ranged from 50 mg to 150 mg) prior to the CBT session. The results in the adult literature has been mixed (see Norberg MM et al, Biol Psychiatry 2008;63:1118–1126). 

CCPR: Thank you, Dr. Rynn.