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Treating Depression without Medication Debra B. Schroeck, MS, PA-C Faculty Instructor Co-Investigator & Sub-Investigator Research & Clinical Psychiatry Physician Assistant UC Department of Psychiatry & Behavioral Neuroscience What is depression? (per DSM-5) • Five (or more) symptoms during the same 2-week period (or longer); including at least (1) depressed mood or (2) loss of interest or pleasure. • (Not to include symptoms due to a general medical condition.) (1) Depressed mood (e.g. feels sad, empty; appears tearful). (Note: In children & adolescents, can be irritable mood.) (2) Markedly diminished interest or pleasure (3) Significant weight loss when not dieting or weight gain or decrease or increase in appetite nearly every day. (Note: In children, consider failure to make expected weight gains.) (4) Difficulty sleeping (insomnia or hypersomnia) (5) Difficulty being still (psychomotor agitation) or feeling slowed down (psychomotor retardation) (6) Loss of energy (fatigue) (7) Feelings of not liking or even hating yourself (worthlessness) or feeling bad about things you do when you shouldn’t feel bad (inappropriate guilt) (8) Difficulty thinking or indecisiveness, (9) Recurrent thoughts of death or suicidal thoughts. The symptoms cause stress that keeps you from doing normal things (impairs functioning). The symptoms are not due to a substance (e.g., street drugs, Rx meds) or another illness (e.g., hypothyroidism). Responses to a significant loss (eg. Grief after death, bankruptcy, following natural disasters, serious illnesses or becoming disabled) may include the feelings of intense sadness, ongoing thoughts about it, difficulty sleeping, poor appetite & weight loss. The presence of MDD in addition to the normal response to a significant loss should be considered. The symptoms are not schizophrenia type illnesses; psychotic disorders; manic or hypomanic episodes (in BP). Psychotherapy: is a general term for treating mental health problems by talking with a psychiatrist, psychologist or other mental health provider. During psychotherapy, one hopes to learn about their condition and moods, feelings, thoughts and behaviors, how to take control of one's life and respond to challenging situations. How the provider responds changes as they acquire experience, knowledge, and insight of the people undergoing treatment. Psychotherapy used for the treatment of major depressive disorder: Behavior therapy Cognitive-behavioral therapy (CBT) Family therapy Group psychotherapy Interpersonal psychotherapy Mindfulness-based cognitive therapy (MBCT) Psychodynamic psychotherapy Supportive psychotherapy In mild cases, psychosocial interventions are often recommended as first-line treatments. The APA guideline supports this approach but notes that combining psychotherapy with antidepressant medication may be more appropriate for patients with moderate to severe major depressive disorder. Behavior therapies use education, guided practice, HW assignments, and positive feedback towards acting more like yourself, over 8-16 weeks. Depressive behaviors such as self-blame, passivity, and negativism are ignored, and behaviors that are more like the opposite of depression, such as activity & experiencing pleasure, are rewarded. Rewards can be anything that the patient seems to seek out -- from attention, to praise, to being permitted to withdraw or complain. Giving the patient small, separate tasks that very gradually become demanding helps turn around learned helplessness. Each positive experience reinforces a feeling of accomplishment that makes the next task easier. Cognitive-behavioral therapy (CBT) was specifically designed to treat depression, and its use in treating major depressive disorder is based on the premise that patients who are depressed have a distorted view of themselves, the world, and the future. These cognitive distortions contribute to their depression and can be identified and counteracted with CBT. Family therapy is an approach to change how families get along, encourage patients to take their meds, and feel better. Families participate in lessons that teach about depression, the patient’s own symptoms, how to prevent future depression, how to improve talking skills between family members, and how to solve family problems. In everyday practice, family involvement is important for most patients with mood disorders, whether or not specific family therapies are employed. Group psychotherapy: one or more therapists treat a small group of clients together as a group. This really can mean any form of psychotherapy when delivered in a group format, including Cognitive Behavioral Therapy or Interpersonal Therapy, but it is usually applied to psychodynamic group therapy where the group context and group process is itself used for change by developing, exploring and examining group relationships. This can be support groups, or skills training groups (such anger management, mindfulness, relaxation training or social skills training), and psycho-education groups. Interpersonal psychotherapy (IPT) is designed to improve depression by enhancing the quality of the patient’s interpersonal world. The treatment begins with an explanation of the diagnosis and options; this is to let people know depression is a real illness. ITP’s focus is on the present. Acute treatment follows a manual based protocol over 12-16 weeks (maintenance IPT is also available.) Homework is assigned. The patient works towards explicit goals related to basic interpersonal problems that are believed to be important (unresolved grief, role disputes, transitions to new roles, and social skills deficits) to improve relationships with others. Role playing & meetings with partners help clarify expectations. Interpersonal Psychotherapy focuses on problem areas of grief, interpersonal roles, disputes, role transitions, and interpersonal difficulties. Mindfulness-based cognitive therapy (MBCT): psychologist John Teasdale & his colleagues augmented cognitive therapy with mindfulness meditation, an ancient practice that cultivates awareness of the present. MBCT doesn’t aim to change the content of thoughts, instead it encourages allowing thoughts & feelings simply to be there. This attitude seeks not to avoid, but rather recognize thoughts that arise. Rather than discouraging painful experience, painful experiences are acknowledged as a part of the stream of consciousness and let go (instead of being ruminated upon). Psychodynamic psychotherapy: focuses on internal conflicts, some of which are unconscious. Yet internal & interpersonal conflicts are thoroughly intertwined: internal conflicts stem largely from interpersonal relationships-most prominently, attachment relationships in childhood-and internal conflicts also contribute to interpersonal conflicts. Psychodynamic psychotherapy aims to unravel such conflicts and thereby alleviate stress & depression. Psychodynamic psychotherapy can be particularly helpful when persistent personality problems perpetuate depression and limit your capacity to benefit from other forms of treatment. You might need a substantial amount of time to develop a relationship that can help solve problems that interfere with treatment. Supportive psychotherapy: is a psychotherapeutic approach that integrates psychodynamic, cognitive-behavioral, and interpersonal conceptual models and techniques. The objective of the therapist is to reinforce the patient's healthy and adaptive patterns of thought behaviors in order to reduce the intrapsychic conflicts that produce symptoms of mental disorders. Unlike in psychoanalysis, in which the analyst works to maintain a neutral demeanor as a "blank canvas" for transference, in supportive therapy the therapist engages in a fully emotional, encouraging, and supportive relationship with the patient as a method of furthering healthy defense mechanisms, especially in the context of interpersonal relationships. (Transference is when a patient attributes to their psychotherapist characteristics from persons in their past, such as their parents.) Electroconvulsive therapy: entails an electrically induced generalized seizure following the administration of a general anesthetic and a muscle relaxant. The typical course of treatment is 3 per week for 2-4 weeks; can be +/-. Bilateral ECT generally has the greater antidepressant effect; unilateral right-hemisphere ECT is less disruptive to memory. Despite its safety & effectiveness, ECT is rarely employed first-line: exceptions are for the extremely ill or suicidal needing a rapid response; when alternative treatments involve higher risk; and when the patient has responded best to it in the past or has a strong preference for it. Continuation and maintenance treatment are often employed, most often with antidepressant medication (though can be ECT.) Transcranial magnetic stimulation (TMS): was approved by the FDA in 2013 for treating MDD when one class of antidepressant has failed. It employs a handheld electromagnetic to induce electrical current in the brain without causing seizures. Depending on the frequency of the current, it either increases or decreases neuronal excitability in the brain region stimulated. A double-blind, multi-center, controlled TMS trial found that 30.4% of patients in the trial’s active treatment group achieved remission from major depression after 5 weeks of TMS treatment. The 233 patients in the trial had previously failed to respond to therapeutic treatments or could not tolerate antidepressant medication because of side effects. Vagus nerve stimulation (VNS): has been approved by the FDA for use in adult patients who have failed to respond to at least 4 adequate medications and/or ECT treatment regimens. A pacemaker-like device is implanted in the body & attached to a stimulating wire that is threaded along the vagus nerve, which travels up the neck to the brain where it connects to areas believed to be involved in regulating mood. Once implanted, it delivers regular electrical impulses to the vagus nerve. These electrical impulses transmitted via the vagus nerve to the brain can relieve the symptoms of depression. They may affect the chemical balance of the brain. Studies show that, on average, it may take up to 9 months for a treatment response to occur. Deep brain stimulation (DBS): appears to be a safe and effective long-term treatment for treatment-resistant depression. A thin electrode about the width of a human hair is inserted directly into the brain. Different currents are applied at varying depths until the desired effects are found. Experience with this invasive technique is limited, however, and the method remains experimental. Because of its invasiveness, DBS will likely be used only for patients who have not responded to less invasive techniques (such as ECT, TMC, & VNS.) Bright-Light Therapy (BLT): is used to treat seasonal affective disorder (SAD) at an intensity of 10,000 lux for 30-90 minutes daily, usually within 1 hour of arising in the morning. BLT may be effective in nonseasonal depression or as an augmenting agent (with antidepressant medication.) Studies have demonstrated benefit of BLT for treatment of nonseasonal depression in pregnant patients and elderly patients. Like any effective antidepressant, BLT has the potential to precipitate a hypomanic or manic episode in susceptible individuals. Other common adverse effects include eye irritation, restlessness, and transient headaches. These lamps are not a significant source of ultraviolet (UV) light. Physical activity (exercise): contributes to recovery from MDD. A meta-anaysis of randomized controlled trials suggested a short-term effect on depression. Experiments in animals suggest an increase in neurogenesis (birth of neurons-- new nerve cells in the brain), and an increased serotonergic drive in response to exercise and that these effects result in an antidepressant action. Nonbiologic pathways considered include: depressed patients lacking regular exercise might get positive feedback from others (particularly if being physically active is deemed as a virtue), leading to increased self-esteem; it may separately create a diversion from negative thoughts. (Serotonin is a chemical created by the human body that works as a neurotransmitter. It is regarded by some researchers as a chemical that is responsible for maintaining mood balance, and that a deficit of serotonin leads to depression.) St. John’s wort (Hypericum perforatum): is an OTC herbal remedy which may act as an SSRI. The common dosage is 300mg 3 times/day with meals (to prevent GI upset). It has not been shown to be effective in major depressive episodes and cannot be recommended first-line for moderate depression. Uses include for mild to moderate depressive symptoms; if no clinical response occurs after 3-6 months, encouraging the use of another medication is recommended. 2011 APA guidelines noted the St. John’s wort might be considered for depression, but evidence for its effectiveness is modest, and more information is needed about its interaction with other drugs. Omega 3 Fatty Acids (Fish Oils with EPA & DHA): are most abundant in cold-water fish such as salmon, sardines, and anchovies. If using capsules look for those with both EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid). Omega 3 supplements may boost the effectiveness of antidepressants. They may provide a stand-alone treatment option if concerned about side effects of antidepressants, such as in older adults, people with multiple medical conditions, and women who are pregnant or nursing. The American Psychiatric Association recommends that all adults eat fish at least twice a week. Take 1-2g of oil per day for depression. Don’t exceed 3g/day, due to increasing risk of a GI bleed & GI upset. L-methylfolate: studied as an adjunct in inadequate responders to SSRI’s (in 75 depressed patients who were stratified by biomarker profiles.) Psychiatric outpatients with SSRI-resistant MDD (DSM-IV criteria) received L-methylfolate 15mg/d for 60 days, placebo for 30 days followed by L-methylfolate 15mg/d for 30 days, or placebo for 60 days. This study suggests that 15mg L-methylfolate added to depression treatment with SSRIs can benefit some patients, particularly those who are obese and those with increased inflammatory markers and certain genotypes. Comment: Trying to capture a patient’s inflammatory status with hsCRP might be particularly promising as treatment resistance is increasingly tied to the presence of a low-grade inflammatory state. (Selective Serotonin Reuptake Inhibitors = SSRI’s) Botox (botulinum toxin A): study of injections into the frown muscles of the forehead in patients with depression to improve depressive symptoms up to 24 weeks, which is longer than the neuromuscular effects of Botox (12 to 16 weeks). Participants received either one Botox injection (BTA) at time point 0, followed by one placebo injection at time point week 12 (BTA-first group) or first a placebo injection followed by Botox (BTA-second group). Only patients in a current depressive episode and Hamilton Depression Rating Scale score (21-item HDRS-21) of 14 or greater were included. Also, patients had to be able to produce moderate-to-severe frown lines, as determined by a 10-point scale. Patients who received Botox (at either time point) showed a robust response that was statistically significant whereas placebo injections had essentially no effect. Even though the cosmetic effects wore off at 12 and 16 weeks, improvement continued for those patients who had received BTA first. Partial Sleep Deprivation (PSD): possible mechanisms explaining the rapid, but transient antidepressant effect of PSD are unknown. Preclinical and clinical studies support a role for brain-derived neurotrophic factor (BDNF) in the pathophysiology of stress-related mood disorders. Furthermore, BDNF seems to be linked to antidepressant action. Serum BDNF was evaluated from 28 patients suffering from MDD, who were naive to PSD therapy at seven different time points within a 32 hour time window before (day 0) and after PSD (day 1). PSD induced a very fast increase in BDNF serum levels at day 1 which parallels clinical findings, since levels increased with decreasing depression scores in all participants. Mediterranean Diet: The aim of this study was to assess the role of a nutritional intervention based on a Mediterranean diet (MeDiet) on plasma brain-derived neurotrophic factor (BDNF) levels. PREvencion Dieta MEDiterranean (PREDIMED) was a randomized clinical trial designed to assess the effect of a Mediterranean diet (MeDiet) on the primary prevention of cardiovascular disease. For this analysis, 243 participants from the Navarra centre were randomly selected. Participants were assigned to one of three dietary interventions: control (low-fat) diet, MeDiet supplemented with virgin olive oil (MeDiet + VOO), or MeDiet supplemented with nuts (MeDiet + Nuts). Plasma BDNF levels were measured after 3 years of intervention. Among participants with prevalent depression at baseline, significantly higher BDNF levels were found for those assigned to the MeDiet + Nuts. S-adenosyl-L-methionine (SAM-e): is a substance made naturally in the body that boosts production of several neurotransmitters-- chemical messengers in the brain-- involved in mood regulation. On its own, it works as well as older tricyclic antidepressants. As an add-on it may boost the effectiveness of an SSRI or SNRI. Adults may benefit from 400 to 1,600mg/day, although some people will need to take 3,000mg per day to alleviate symptoms. Combining SAM-e with an antidepressant is generally safe, but in very rare cases may cause serotonin syndrome-- a potentially deadly complication that causes agitation, anxiety, confusion, nausea, vomiting and palpitations. Acupuncture: evaluation of this intervention for depression is difficult due to it being a complex intervention, and the specific treatment for patients with similar presenting complaints may differ. Results have been mixed. At least one rigorous study of 41 patients showed an equivalent effect between acupuncture and the tricyclic antidepressant amitriptyline. Another study of MDD in 61 pregnant women compared acupuncture specifically tailored to treat depression, general acupuncture that didn’t target depression, or massage therapy. Additional studies should be done before acupuncture can be recommended as an effective treatment for depression. Melatonin (N-acetyl-5-methoxytryptamine): suggested dosing for winter depression is 0.125mg twice per day. It is a hormone produced by the pineal gland; regulates sleep cycle. It is suggested as useful for circadian rhythm sleep disorders; helpful for sleep-wake cycle disorders. Possible side effects: abdominal cramps, alertness decreased, circadian rhythm disruption, daytime fatigue, depression (transient) dizziness, drowsiness, dysphoria in depressed patients, headache & irritability. The pineal gland secretes less melatonin when exposed to bright light; therefore, the level of this chemical is lowest during the daytime hours of wakefulness. Do not use with sodium oxybate; see other interactions. Questions?