Cln&Aggr

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Cln&Aggr
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Clonidine & Clonicel

Table of Contents

There is currently no FDA approved medication for the treatment of aggression. Beta blockers such as propranolol have shown some usefulness as reviewed by Connor D.F. (1993). Lithium (Campbell, M., 1995) and Carbamazepine (Silva P.R., 1996) have also been used, among many others. Kemph and colleagues (1993) found clonidine to be significantly effective in reducing symptoms in overly aggressive children. Clonidine may thus hold promise as one of the few medications helpful in treating aggression.

Autism

Many autistic children have associated problems of inattention, impulsivity, hyperactivity and aggressivity that limit the feasibility or effectiveness of educational and behavioral interventions. Clonidine has been shown to be helpful in reducing these symptoms. Jaselskis and colleagues (1992) examined autistic children with excessive inattention, impulsivity, and hyperactivity and oppositionality. Subjects that had not tolerated or responded to neuroleptics, methylphenidate, or desipramine showed significant improvement with clonidine treatment.

Anxiety Disorders

Generalized Anxiety Disorder (GAD)

Symptoms of generalized anxiety disorder (GAD) such as palpitations, shortness of breath, sweating, dry mouth, hot flashes, abdominal distress and trouble swallowing may be due to sympathetic autonomic hyperactivity. For some time the Beta receptor blocking agents such as propranolol (Inderal) have
been shown to decrease such symptoms, especially those involving peripheral adrenergic over excitation. Clonidine also shows a muting of the autonomic manifestations of anxiety, and appears to have central effects as well. Clonidine's effect in decreasing anxiety appears independent of its sedative properties. Clonidine has an advantage over the beta blockers in patients with asthma. The alpha agonists do not pose the risk that the beta blockers do in precipitating an asthma attack.

Social Phobia and Selective Mutism

Seriously symptomatic patients with social phobia suffer from marked anxiety in social situations. It is believed that the anxiety symptoms are likely mediated by an adrenergic hyperactivity. According to Marshall (1993), studies of clonidine efficacy in treating social phobia have had mixed results. This may be due to problems in using the short acting tablet of clonidine which has the potential for producing a rebound anxiety when it suddenly wears off. I have found in my practice that extended release forms of clonidine appear to provide more consistent results in treating social phobias and in cases of selective mutism. Clonidine may also be used in combination with other medications such as the SSRIs (Zoloft), the benzodiazepines (Xanax) chlomipramine (Anafranil) and buspirone (Buspar).

Panic Disorder

Liebowitz and Colleagues (1981) found clonidine to be effective in treating both panic disorder and panic attacks with agoraphobia. Uhde and colleagues (1989) found the antipanic effect did not persist in their study subjects clonidine potential efficacy is based on the possibility that panic disorder is a dysregulation of brain alpha-2 adrenoceptor sensitivity.

It is unclear why an initial antipanic effect would not be sustained. The clonidine dose may need to be increased periodically to maintain an antipanic effect.

This has been found to be the case when treating many conditions with clonidine and other drugs that are metabolized by the liver. The rapid initial tolerance that appears to slowly "plateau" after a few weeks or months is most likely due to initial increase in liver enzymes that speeds up the clearance of clonidine.

Other limitations of clonidine in panic may be due to its rebound hyperarousal often experienced when the short acting oral tablet dose quickly wears off. Rebound hyperarousal could contribute to precipitation's of panics. If this were the case, the extended release formulations of clonidine would be expected to more clearly provide sustained benefit (see section on Clonicel ® in this chapter).

Post-Traumatic Stress Disorder (PTSD)

   Genetic studies by Comings and colleagues (1996) examined Vietnam veterans on an addiction treatment unit who had been exposed to severe combat conditions. They found that a DRD2 variant appeared to confer an increased risk for post traumatic stress disorder (PTSD). The absence of the variant of the gene for making the dopamine receptor was associated with a relative resistance. This suggested that dopamine receptors play a role in PTSD. PTSD symptoms are believed to be also related to noradrenergic hyperarousal, as Nutt (1989) and others (Southwick, S.M., 1993) have explained. Orr SP, and colleagues (1995) found abnormal physiologic responses to loud tones in Vietnam veterans with post traumatic stress disorder.
   Such studies would suggest a potential benefit from treatment with clonidine.    Clonidine has been used to treat Cambodian patients with   post-traumatic stress disorder (Kinzie JD, Leuing P. 1989). Hansenne and colleagues (1991) explored the use of clonidine response as a test in evaluating post-traumatic stress.
   I have found clonidine useful in my practice as an adjunctive treatment to diminish some of the physiologic hyperreactivity that occurs upon exposure to events that trigger PTSD symptoms. I have found similar benefit from clonidine in treating dissociative disorders such as multiple personality disorder, when related to past traumatic events The diminution of a conditioned or sensitized autonomic responsivity serves to make memories that induce fear and panic easier to access and detoxify.

Bipolar Disorder (Manic Depressive Illness)

Lithium remains the first line and most effective medication for treating bipolar disorder. Other medications found to be effective include Valproate and Tegretol. Based on the catecholamine hypothesis of mood disorders, the manic phase of bipolar disorder may reflect an extreme state of noradrenergic hyperactivity. A subduing effect on mania by clonidine would certainly support this view. Clonidine has shown some efficacy in treating the manic and mixed phases of bipolar disorder, with minimal side effects (Kontaxakis et al. 1989).

Post Traumatic Brain Injury (TBI)

There is a broad spectrum of neurophysiological symptoms that characterize the post traumatic brain injury (TBI) syndrome (Gualtieri, 1990).
Manic syndromes can follow various brain injuries and can greatly complicate rehabilitation and treatment outcome (Starkstein, et al., 1988). Bakchine (1989) and other researchers noted that after brain injury there is an increase in noradrenergic transmission that could be a factor in the precipitation of organic mania. The longer term adverse outcome of an under aroused brain often seen in post traumatic TBI may result from a resetting of brain receptor sensitivity as a consequence of such a massive noradrenergic outpouring immediately following the injury. This may explain why noradrenergic stimulants like the amphetamines have been particularly useful in TBI rehabilitation after the acute stages resolve. Clonidine has also shown usefulness in the rapid reversal of the manic symptoms in patients with focal brain damage, especially after bilateral frontal or right temporoparietal lobe lesions.

Psychosis

Several studies have documented the effectiveness of clonidine in treating certain types of schizophrenia characterized by problems with arousal. Clonidine's efficacy supports a role for noradrenaline in the etiology of schizophrenia. It is not surprising that paranoid schizophrenia responds the most to treatment with clonidine as this the paranoid state is one involving extremely high noradrenergic states similar to those noted in mania. Clonidine may not be a good antipsychotic per se, but may contribute to stabilizing the over aroused, paranoid aspects of the psychosis. In doing so, clonidine might indirectly enhance the effectiveness of an antipsychotic medication.